Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H (HLA-H). HLA-H (also known as hereditary hemochromatosis protein; HFE) is a major histocompatibility complex (MHC) class I-like protein that is mutated in Hereditary Hemochromatosis. HFE is a protein of 343 amino acids that includes a signal peptide, an extracellular transferrin receptor-binding region (a1 and a2), an immunoglobulin-like domain (a3), a transmembrane region, and a short cytoplasmic tail. HFE binds beta-2-microglobulin to form a heterodimer expressed at the cell surface. It binds transferrin receptor (TFRC) in its extracellular alpha1-alpha2 domain. HFE plays an important part in the regulation of hepcidin expression in response to iron overload and the liver is important in the pathophysiology of HFE-associated hemochromatosis. Nine HFE splicing variants have been reported with transcripts lacking exon 2 or exon 3, or exons 2-3, 2-4, or 2-5. Diverse mutations involving HFE introns and exons discovered in persons with hemochromatosis or their family members cause or probably cause high iron phenotypes. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 113 KVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQV 192
Cdd:cd21021   2 QVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQV 81

                        90
                ....*....|...
gi 21040343 193 EHPGLDQPLIVIW 205
Cdd:cd21021  82 EHPGLDQPLIVIW 94

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H (HLA-H). HLA-H (also known as hereditary hemochromatosis protein; HFE) is a major histocompatibility complex (MHC) class I-like protein that is mutated in Hereditary Hemochromatosis. HFE is a protein of 343 amino acids that includes a signal peptide, an extracellular transferrin receptor-binding region (a1 and a2), an immunoglobulin-like domain (a3), a transmembrane region, and a short cytoplasmic tail. HFE binds beta-2-microglobulin to form a heterodimer expressed at the cell surface. It binds transferrin receptor (TFRC) in its extracellular alpha1-alpha2 domain. HFE plays an important part in the regulation of hepcidin expression in response to iron overload and the liver is important in the pathophysiology of HFE-associated hemochromatosis. Nine HFE splicing variants have been reported with transcripts lacking exon 2 or exon 3, or exons 2-3, 2-4, or 2-5. Diverse mutations involving HFE introns and exons discovered in persons with hemochromatosis or their family members cause or probably cause high iron phenotypes. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 113 KVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQV 192
Cdd:cd21021   2 QVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQV 81

                        90
                ....*....|...
gi 21040343 193 EHPGLDQPLIVIW 205
Cdd:cd21021  82 EHPGLDQPLIVIW 94

Class I Histocompatibility antigen, domains alpha 1 and 2;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343    27 SHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDH--ESRRVEPRTPWVsSRISSQMWLQLSQSLKGWDHMFTVDFWT 104
Cdd:pfam00129   2 SHSLRYFYTAVSRPGLGEPRFIAVGYVDDTQFVRFDSdaANPRMEPRAPWI-EQEGPEYWERETQIAKGNEQIFRENLRT 80

                  ....*....
gi 21040343   105 IMENHNHSK 113
Cdd:pfam00129  81 LLGYYNQSE 89

MHC-like TNF binding protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343   41 DLGlSLFEALGYV--DDQLFVFYDHESRR---VEPRT-PWVSS-RISSQMWLQLSQSLKGWDHM---FTV-DFWTIMENH 109
Cdd:PHA02865 119 DLG-QLFGSFGYVevAGGILARFDTKNKRftkVTSKGfPKVGMlTVKSPFWKDVMKYLGSFVYLtcgLTAnDYQKMAKGN 197

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 21040343  110 NHSKVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKW--LKDKQP 153
Cdd:PHA02865 198 IPKPVTPTVKVTGEELGDNTTLFCTFDSHYPSSVAAKWynSEDFAP 243

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H (HLA-H). HLA-H (also known as hereditary hemochromatosis protein; HFE) is a major histocompatibility complex (MHC) class I-like protein that is mutated in Hereditary Hemochromatosis. HFE is a protein of 343 amino acids that includes a signal peptide, an extracellular transferrin receptor-binding region (a1 and a2), an immunoglobulin-like domain (a3), a transmembrane region, and a short cytoplasmic tail. HFE binds beta-2-microglobulin to form a heterodimer expressed at the cell surface. It binds transferrin receptor (TFRC) in its extracellular alpha1-alpha2 domain. HFE plays an important part in the regulation of hepcidin expression in response to iron overload and the liver is important in the pathophysiology of HFE-associated hemochromatosis. Nine HFE splicing variants have been reported with transcripts lacking exon 2 or exon 3, or exons 2-3, 2-4, or 2-5. Diverse mutations involving HFE introns and exons discovered in persons with hemochromatosis or their family members cause or probably cause high iron phenotypes. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 113 KVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQV 192
Cdd:cd21021   2 QVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQV 81

                        90
                ....*....|...
gi 21040343 193 EHPGLDQPLIVIW 205
Cdd:cd21021  82 EHPGLDQPLIVIW 94

Immunoglobulin domain of Zn-alpha2-glycoprotein (ZAG); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Zn-alpha2-glycoprotein (ZAG). ZAG is a soluble protein that is present in serum and other body fluids. ZAG stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. The 2.8 angstrom crystal structure of ZAG resembles a class I major histocompatibility complex (MHC) heavy chain, but ZAG does not bind the class I light chain beta-2-microglobulin. The ZAG structure includes a large groove analogous to class I MHC peptide binding grooves. Instead of a peptide, the ZAG groove contains a nonpeptidic compound that may be implicated in lipid catabolism under normal or pathological conditions. IgC_MHC_I_alpha3; Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 115 PPLVKVTHHVT-SSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEpkDVLPNGDGTYQGWITLAVPPGEEQRYTCQVE 193
Cdd:cd21010   4 PPSVSVTSHVApGKNRTLKCLAYDFYPRGISLHWTRAGKVQESESGG--DVLPSGNGTYQSWVVVEVPPQDRAPYSCHVE 81

                        90
                ....*....|..
gi 21040343 194 HPGLDQPLIVIW 205
Cdd:cd21010  82 HSSLAQPLTVPW 93

Immunoglobulin domain of Cluster of Differentiation (CD) 1; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Cluster of Differentiation (CD) 1. CD1 family of transmembrane glycoproteins, are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. They mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes (CD1a, CD1b, CD1c, CD1d, and CD1e) organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. CD1a localizes to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells. C1-set Ig domains have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 114 VPPLVKVTHH--VTSSVTTLRCRALNYYPQNITMKWLKDKQPMDaKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQ 191
Cdd:cd21029   1 VKPRVRLSSRpsPGDGHLQLSCHVTGFYPRPIEVTWLRDGQEQM-DGTQSGGILPNHDGTYQLRKTLDIAPGEGAGYSCR 79

                        90
                ....*....|....
gi 21040343 192 VEHPGLDQPLIVIW 205
Cdd:cd21029  80 VDHSSLKQDLIVYW 93

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-1 and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-1 and similar proteins. Qa-1 presents hydrophobic peptides including Qdm derived from the leader sequence of classical MHC I molecules for immune surveillance by NK cells. Qa-1 bound peptides derived from the TCR Vbeta8.2 of activated T cells also activates CD8+ regulatory T cells to control autoimmunity and maintain self-tolerance. Four allotypes of Qa-1 (Qa-1a-d) are expressed that are highly conserved in sequence but have several variations that could affect peptide binding to Qa-1 or TCR recognition. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 115 PPLVKVTHHVTSS-VTTLRCRALNYYPQNITMKWLKDKQPMdAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVE 193
Cdd:cd21013   4 PPKAHVTHHPRSEgYVTLRCWALGFYPADITLTWQLNGEEL-TQDMEFVETRPAGDGTFQKWASVVVPLGKEQKYTCHVE 82

                        90
                ....*....|....
gi 21040343 194 HPGLDQPLIVIWEP 207
Cdd:cd21013  83 HEGLPEPLTLRWEP 96

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) G; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) G. HLA-G histocompatibility antigen (also known as human leukocyte antigen G ; HLA-G) is a protein that in humans is encoded by the HLA-G gene. HLA-G belongs to the HLA nonclassical class I heavy chain paralogs. This class I molecule is a heterodimer consisting of a heavy chain and light chain, beta-2-microglobulin. The heavy chain is anchored in the membrane. HLA-G may play a role in immune tolerance in pregnancy, being expressed in the placenta by extravillous trophoblast cells (EVT), while the classical MHC class I genes (HLA-A and HLA-B) are not. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I and class II. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells. MHC class II molecules play a key role in the initiation of the antigen-specific immune repose. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 115 PPLVKVTHH-VTSSVTTLRCRALNYYPQNITMKWLKDKQPmDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVE 193
Cdd:cd21022   4 PPKTHVTHHpVFDYEATLRCWALGFYPAEIILTWQRDGED-QTQDVELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQ 82

                        90
                ....*....|..
gi 21040343 194 HPGLDQPLIVIW 205
Cdd:cd21022  83 HEGLPEPLMLRW 94

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) A; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) A. The classical class I molecules (HLA-A, -B, and -C) are responsible for the presentation of endogenous antigen to CD8+ T cells. The receptor is a heterodimer, and is composed of a heavy alpha chain and smaller beta chain. The alpha chain is encoded by a variant HLA-A gene, and the beta chain (beta-2-microglobulin) is an invariant beta-2-microglobulin molecule. The beta-2-microglobulin protein is coded for by a separate region of the human genome. HLA-A2 is associated with spontaneous abortions, HIV, and Hodgkin lymphoma. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 116 PLVKVTHH-VTSSVTTLRCRALNYYPQNITMKWLKDKQPmDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEH 194
Cdd:cd21027   6 PKTHMTHHaVSDHEATLRCWALSFYPAEITLTWQRDGED-QTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYTCHVQH 84

                        90
                ....*....|.
gi 21040343 195 PGLDQPLIVIW 205
Cdd:cd21027  85 EGLPKPLTLRW 95

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of MIC-A and MIC-B; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of MIC-A and MIC-B. MIC-A and MIC-B are homologs that serve as stress-inducible antigens on epithelial and epithelially derived cells. Both serve as ligands for the widely expressed activating immunoreceptor NKG2D, a C-type lectin-like activating immunoreceptor. MIC-B is very similar in structure to MIC-A and likely interacts with NKG2D in an analogous manner. The interdomain flexibility observed in the MIC-A structures, a feature unique to MIC proteins among MHC class I proteins and homologs, is also displayed by MIC-B, with an interdomain relationship intermediate between the two examples of MIC-A structures. Mapping sequence variations onto the structures of MIC-A and MIC-B reveals patterns completely distinct from those displayed by classical MHC class I proteins, with a number of substitutions falling on positions likely to affect interactions with NKG2D, but with other positions lying distant from the NKG2D binding sites or buried within the core of the proteins. Members of the IgC family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding and the IgC domain is involved in oligomerization and molecular interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 114 VPPLVKVT-HHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQV 192
Cdd:cd21017   3 VPPMVNVTrSEASEGNITVTCRASGFYPWNITLSWRQDGVSLSHDTQQWGDVLPDGNGTYQTWVATRICQGEEQRFTCYM 82

                ....
gi 21040343 193 EHPG 196
Cdd:cd21017  83 EHSG 86

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-2; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of QA-2. Qa-2 is a nonclassical MHC Ib antigen, which has been implicated in both innate and adaptive immune responses, as well as embryonic development. Qa-2 has an unusual peptide binding specificity in that it requires two dominant C-terminal anchor residues and is capable of associating with a substantially more diverse array of peptide sequences than other nonclassical MHC. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 115 PPLVKVTHHVTS-SVTTLRCRALNYYPQNITMKWLKDKQPMdAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVE 193
Cdd:cd21014   4 PPKAHVTHHPRSyGAVTLRCWALGFYPADITLTWQLNGEEL-TQDMELVETRPAGDGTFQKWASVVVPLGKEQNYTCHVN 82

                        90
                ....*....|..
gi 21040343 194 HPGLDQPLIVIW 205
Cdd:cd21014  83 HEGLPEPLTLRW 94

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of H2-Dd; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of H2-Dd. Mouse MHC is composed of 11 subclasses. It includes the classical MHC class I (MHC-Ia) that comprises H-2D, H-2K and H-2L subclasses, the non-classical MHC class I (MHCIb) that comprises H-2Q, H-2M and H-2T subclasses, the classical MHC class II (MHC-IIa) that includes H-2A(I-A) and H-2E(I-E) subclasses, and the non-classical MHC class II (MHC-IIb) comprises H-2M and H-2O. H-2K, H-2D, and H-2L are 80 to 90% homologous at the amino acid level yet appear to be involved in different recognition reactions and are differentially expressed on lymphoid cells. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 115 PPLVKVTHHV-TSSVTTLRCRALNYYPQNITMKWLKDKQPMdAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVE 193
Cdd:cd21020   5 PPKAHVTHHRrPEGDVTLRCWALGFYPADITLTWQLNGEEL-TQEMELVETRPAGDGTFQKWASVVVPLGKEQKYTCHVE 83

                        90
                ....*....|..
gi 21040343 194 HPGLDQPLIVIW 205
Cdd:cd21020  84 HEGLPEPLTLRW 95

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of RT1-Aa; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of RT1-Aa. While most mammalian species transport these peptides into the ER via a single allele of TAP, rats have evolved different TAPs, TAP-A and TAP-B, RT1-Aa and RT1-A1c, which are associated with TAP-A and TAP-B. The rat MHC class Ia molecule RT1-Aa has the unusual capacity to bind long peptides ending in arginine, such as MTF-E, a thirteen-residue, maternally transmitted minor histocompatibility antigen. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 115 PPLVKVT-HHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMdAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVE 193
Cdd:cd21015   4 PPEAHVTlHPRPEGDVTLRCWALGFYPADITLTWQLNGEDL-TQDMELVETRPAGDGTFQKWASVVVPLGKEQNYTCRVE 82

                        90
                ....*....|...
gi 21040343 194 HPGLDQPLIVIWE 206
Cdd:cd21015  83 HEGLPKPLSQRWE 95

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 119 KVTHHVTSS------VTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPkDVLPNGDGTYQGWITLAVPPGEEQ---RYT 189
Cdd:cd00098   1 TVTLLPPSPeekgggKVTLVCLVSGFYPKDITVTWLKNGVPLTSGVSTS-SPVEPNDGTYSVTSSLTVPPSDWDegaTYT 79

                        90
                ....*....|....*.
gi 21040343 190 CQVEHPGLDQPLIVIW 205
Cdd:cd00098  80 CVVTHESLKSPLSKTW 95

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II beta chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain has two globular domains (N- and C-terminal) and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 113 KVPPLVKVTHHVT---SSVTTLRCRALNYYPQNITMKWLKDKQpMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYT 189
Cdd:cd05766   1 RVQPSVKVSPTKTgplEHPNLLVCSVTGFYPAEIEVKWFRNGQ-EETAGVVSTELIPNGDWTFQILVMLETTPRRGDVYT 79

                        90
                ....*....|....*..
gi 21040343 190 CQVEHPGLDQPLIVIWE 206
Cdd:cd05766  80 CQVEHSSLQSPLTVDWR 96

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 21040343    130 TLRCRALNYYPQNITMKWLKDKQPMdAKEFEPKDVLPNGDGTYQGWITLAVP---PGEEQRYTCQVEHPGLDQP 200
Cdd:smart00407   3 TLVCLVSGFYPPDITVTWLRNGQEV-TEGVSTTDPLKNSDGTYFLSSYLTVPastWESGDVYTCQVTHEGLKEP 75

Tapasin-R immunoglobulin-like domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain on Tapasin-R. Tapasin is a V-C1 (variable-constant) immunoglobulin superfamily molecule present in the endoplasmic reticulum (ER), where it links MHC class I molecules to the transporter associated with antigen processing (TAP). Tapasin-R is a tapasin-related protein that contains similar structural motifs to Tapasin, with some marked differences, especially in the V domain, transmembrane and cytoplasmic regions. The majority of Tapasin-R is located within the ER; however, there may be some expression of Tapasin-R at the cell surface. Tapasin-R lacks an obvious ER retention signal.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 130 TLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVL-----PNGDGTYQGWITLAVPPGEEQR---YTCQVEHPGLDQPL 201
Cdd:cd05771  18 TLSCHIAGYYPLDVDVEWLREEPGGSESQVSRDGVSlsshrQSVDGTYSISSYLTLEPGTENRgatYTCRVTHVSLEEPL 97

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21040343   130 TLRCRALNYYPQNITMKWLKDKQPM--DAKEFEPkdvLPNGDGTYQGWITLAVPPGEEQR---YTCQVEHPGL 197
Cdd:pfam07654  16 TLTCLVTGFYPPDITVTWLKNGQEVteGVKTTPP---SPNSDWTYQLSSYLTVTPSDWESgdeYTCRVEHEGL 85

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR. HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. HLA-DR is also involved in several autoimmune conditions, disease susceptibility, and disease resistance including seronegative-rheumatoid arthritis, penicillamine-induced myasthenia, schizophrenia, Goodpasture syndrome, systemic lupus erythematosus, Alzheimers, tuberculoid leprosy, and Hashimoto's thyroiditis. HLA-DR molecules are upregulated in response to signaling. HLA-DR is an alphabeta heterodimer cell surface receptor, each subunit of which contains two extracellular domains, a membrane-spanning domain, and a cytoplasmic tail. Both alpha and beta chains are anchored in the membrane. The DR beta chain is encoded by 4 loci, however no more than 3 functional loci are present in a single individual, and no more than two on a single chromosome. Sometimes an individual may only possess 2 copies of the same locus, DRB1*. The HLA-DRB1 locus is ubiquitous and encodes a very large number of functionally variable gene products (HLA-DR1 to HLA-DR17). The HLA-DRB3 locus encodes the HLA-DR52 specificity, is moderately variable and is variably associated with certain HLA-DRB1 types. The HLA-DRB4 locus encodes the HLA-DR53 specificity, has some variation, and is associated with certain HLA-DRB1 types. The HLA-DRB5 locus encodes the HLA-DR51 specificity, which is typically invariable, and is linked to the HLA-DR2 types. Three genetically distinct isotypes of class II MHC molecules are found in humans (HLA-DR, HLA-DQ, and HLA-DP), and two in mice (I-E and I-A). MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 112 SKVPPLvkvTHHvtssvTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEpKDVLPNGDGTYQGWITLAVPPGEEQRYTCQ 191
Cdd:cd21000  11 AKTQPL---QHH-----NLLVCSVNGFYPGSIEVRWFRNGQEEKAGVVS-TGLIQNGDWTFQTLVMLETVPRSGEVYTCQ 81

                        90
                ....*....|....
gi 21040343 192 VEHPGLDQPLIVIW 205
Cdd:cd21000  82 VEHPSVTSPLTVEW 95

Signal-regulatory protein (SIRP) immunoglobulin-like domain 3; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in Signal-Regulatory Protein (SIRP), domain 3 (C1 repeat 2). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three Immunoglobulin superfamily domains a single V-set and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions that have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs but also binds CD47, but with much less affinity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 114 VPPLVKVTHHVTS--SVTTLRCRALNYYPQNITMKWLKDKQPMDAKefEPKDVLPNGDGTY--QGWITLAVPPGEEQ-RY 188
Cdd:cd16085   1 VPPTLEVTQQPTMvwNQVNVTCQVEKFYPQRLQLTWLENGNVSRTE--TPSTLTVNKDGTYnwTSWLLVNVSAHREDvVL 78

                        90
                ....*....|....
gi 21040343 189 TCQVEHPGldQPLI 202
Cdd:cd16085  79 TCQVEHDG--QPAV 90

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DP; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DP. HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the HLA-DPB1 gene. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DP is an alphabeta heterodimer cell-surface receptor. Each DP subunit (alpha-subunit, beta-subunit) is composed of a alpha-helical N-terminal domain, an IgG-like beta sheet, a membrane spanning domain, and a cytoplasmic domain. The alpha-helical domain forms the sides of the peptide binding groove. The beta sheet regions form the base of the binding groove and the bulk of the molecule as well as the inter-subunit (non-covalent) binding region. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 113 KVPPLVKVT--------HHvtssvTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEpKDVLPNGDGTYQGWITLAVPPGE 184
Cdd:cd21003   1 RVQPKVNVSpskkgplqHH-----NLLVCHVTDFYPGNIQVRWFLNGQEETAGVVS-TNLIHNGDWTFQILVMLEMTPQQ 74

                        90       100
                ....*....|....*....|.
gi 21040343 185 EQRYTCQVEHPGLDQPLIVIW 205
Cdd:cd21003  75 GDVYTCQVEHPSLDSPVTVEW 95

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) DR; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II alpha chain of histocompatibility antigen (HLA) DR. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DR is a cell surface receptor protein found on antigen presenting cells. It is an alphabeta heterodimer of type MHC class II. The alpha and beta chains are encoded by two loci, HLA-DRA1 and HLA-DRB1, that are adjacent to each other on chromosome band 6p21.31. Susceptibility to multiple sclerosis and rheumatoid arthritis are associated with the human histocompatibility leukocyte antigen HLA-DR2 and HLA-DR4, respectively. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 114 VPPLVKVthhVTSSVTTLR------CRALNYYPQNITMKWLKDKQPMDAKEFEPKdVLPNGDGTYQGWITLAVPPGEEQR 187
Cdd:cd21007   1 VPPEVTV---LTNSPVELRepnvliCFIDKFTPPVVNVTWLRNGKPVTTGVSETV-FLPREDHLFRKFHYLPFLPSTEDV 76

                        90
                ....*....|....*....
gi 21040343 188 YTCQVEHPGLDQPLIVIWE 206
Cdd:cd21007  77 YDCRVEHWGLDEPLLKHWE 95

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) DQ and related proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II alpha chain of histocompatibility antigen (HLA) DQ. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DQ (DQ) is a cell surface receptor protein found on antigen presenting cells. It is an alphabeta heterodimer of type MHC class II. The alpha and beta chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. A person often produces two alpha-chain and two beta chain variants and thus 4 isoforms of DQ. Two autoimmune diseases in which HLA-DQ is involved are celiac disease and diabetes mellitus type 1. DQ is one of several antigens involved in rejection of organ transplants. DQ8 is a split antigen of the DQ3 broad antigen. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 21040343 130 TLRCRALNYYPQNITMKWLKDKQPMdAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWE 206
Cdd:cd21008  20 TLICLVDNIFPPVINITWLSNGHSV-TEGVSETSFLSKSDHSFLKISYLTFLPSADDIYDCKVEHWGLDKPLLKHWE 95

CH3 domain (third constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, gamma, and delta chains, and CH4 domain (fourth constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, epsilon, and mu chains; member of the C1-set of I; The members here are composed of the third and fourth immunoglobulin constant domain (IgC) of alpha, delta, gamma and alpha, epsilon, and mu heavy chains, respectively. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 21040343 130 TLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQR---YTCQVEHPGLDQPLIV 203
Cdd:cd05768  20 TLTCLVKGFYPEDIFVSWLQNGEPLPSADYKTTAPVPESDGSFFVYSKLNVSTADWNSgdvFSCVVGHEALPLQFTQ 96

Immunoglobulin light chain Constant domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) light chain constant (C) domain. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determine the type of immunoglobulin: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343 125 TSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVlPNGDGTYQGWITLAVPPGE---EQRYTCQVEHPGLDQPL 201
Cdd:cd07699  15 SSGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTE-QQSDNTYSMSSYLTLSSSDwnkHKVYTCEVTHEGLSSTI 93

MHC-like TNF binding protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21040343   41 DLGlSLFEALGYV--DDQLFVFYDHESRR---VEPRT-PWVSS-RISSQMWLQLSQSLKGWDHM---FTV-DFWTIMENH 109
Cdd:PHA02865 119 DLG-QLFGSFGYVevAGGILARFDTKNKRftkVTSKGfPKVGMlTVKSPFWKDVMKYLGSFVYLtcgLTAnDYQKMAKGN 197

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 21040343  110 NHSKVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKW--LKDKQP 153
Cdd:PHA02865 198 IPKPVTPTVKVTGEELGDNTTLFCTFDSHYPSSVAAKWynSEDFAP 243

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) I-E; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II alpha chain of histocompatibility antigen (HLA) I-E. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21040343 131 LRCRALNYYPQNITMKWLKDKQPMDAKEFEPKdVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWE 206
Cdd:cd21005  21 LICFIDKFSPPVVNVTWLRNGRPVTEGVSETV-FLPRDDHLFRKFHYLTFLPSTDDFYDCEVDHWGLEEPLRKHWE 95

CH3 domain (third constant Ig domain of the heavy chain) in immunoglobulin delta chain; member of the C1-set of Ig superfamily domains; The members here are composed of the third immunoglobulin constant domain (IgC) of delta heavy chains. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. C1-set Ig domains have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 21040343 131 LRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNG-DGTYQGWITLAVP-PGEEQ--RYTCQVEH 194
Cdd:cd16094  19 LLCEVSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPgSTTFWAWSVLRVPaPPSPQpaTYTCVVSH 86

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy mu chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin constant-1 set domain of mu chains. It belongs to a family composed of the first immunoglobulin constant-1 set domain of alpha, delta, epsilon, gamma, and mu heavy chains. This domain is found on the Fab antigen-binding fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 21040343 125 TSSVTTLRCRALNYYPQNITMKWLKDKQPM--DAKEFEPkdVLPNgdGTYQGWITLAVPPGE---EQRYTCQVEHPG 196
Cdd:cd21819  14 TSDPVTVGCLATDFLPDSITFSWTDDNNSLttGVKTYPS--VLTG--GTYTASSQLQVPESEwksKENFYCKVEHPG 86