Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) beta chain; The members here are composed of the immunoglobulin (Ig) variable domain of the beta chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. This group includes the variable domain of the alpha chain of alpha/beta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635  23 IYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQQDPGMELHLIHYSYGVNSTEKGDLS-SESTVSRIRTEHFPLTLESAR 101
Cdd:cd05899     1 VTQSPRYLIKRRGQSVTLRCSQKSGHDNMYWYRQDPGKGLQLLFYSYGGGLNEEGDLPgDRFSASRPSLTRSSLTIKSAE 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1859675635 102 PSHTSQYLCASSEARGlaefTDTQYFGPGTRLTV 135
Cdd:cd05899    81 PEDSAVYLCASSLGGG----ADEAYFGPGTRLTV 110

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) beta chain; The members here are composed of the immunoglobulin (Ig) variable domain of the beta chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. This group includes the variable domain of the alpha chain of alpha/beta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635  23 IYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQQDPGMELHLIHYSYGVNSTEKGDLS-SESTVSRIRTEHFPLTLESAR 101
Cdd:cd05899     1 VTQSPRYLIKRRGQSVTLRCSQKSGHDNMYWYRQDPGKGLQLLFYSYGGGLNEEGDLPgDRFSASRPSLTRSSLTIKSAE 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1859675635 102 PSHTSQYLCASSEARGlaefTDTQYFGPGTRLTV 135
Cdd:cd05899    81 PEDSAVYLCASSLGGG----ADEAYFGPGTRLTV 110

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635  162 KATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPqPLKEqpalNDSRYCLSSRLRVSATFWqNPRNHFRCQVQFYGLSE 241
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTD-PLKN----SDGTYFLSSYLTVPASTW-ESGDVYTCQVTHEGLKE 74

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635   27 PRYLVIGTGKKITLECS-QTMGHDKMYWYQQDPgmelHLIHYSYGVNSTEKGDLSSestvsrirtehfpLTLESARPSHT 105
Cdd:smart00410   1 PPSVTVKEGESVTLSCEaSGSPPPEVTWYKQGG----KLLAESGRFSVSRSGSTST-------------LTISNVTPEDS 63

                           90       100       110
                   ....*....|....*....|....*....|
gi 1859675635  106 SQYLCAssearglAEFTDTQYFGpGTRLTV 135
Cdd:smart00410  64 GTYTCA-------ATNSSGSASS-GTTLTV 85

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) beta chain; The members here are composed of the immunoglobulin (Ig) variable domain of the beta chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. This group includes the variable domain of the alpha chain of alpha/beta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635  23 IYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQQDPGMELHLIHYSYGVNSTEKGDLS-SESTVSRIRTEHFPLTLESAR 101
Cdd:cd05899     1 VTQSPRYLIKRRGQSVTLRCSQKSGHDNMYWYRQDPGKGLQLLFYSYGGGLNEEGDLPgDRFSASRPSLTRSSLTIKSAE 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1859675635 102 PSHTSQYLCASSEARGlaefTDTQYFGPGTRLTV 135
Cdd:cd05899    81 PEDSAVYLCASSLGGG----ADEAYFGPGTRLTV 110

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635 147 VAVFEPSEAEISHtqKATLVCLATGFYPDHVELSWWVNGKEVHSGV-STDPQPLKeqpalnDSRYCLSSRLRVSATFWqN 225
Cdd:pfam07654   1 VYVFPPSPEELGK--PNTLTCLVTGFYPPDITVTWLKNGQEVTEGVkTTPPSPNS------DWTYQLSSYLTVTPSDW-E 71

                          90
                  ....*....|....
gi 1859675635 226 PRNHFRCQVQFYGL 239
Cdd:pfam07654  72 SGDEYTCRVEHEGL 85

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 1859675635 146 EVAVFEPSEAEIShTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKeqpalNDSRYCLSSRLRVSATFWqN 225
Cdd:cd00098     1 TVTLLPPSPEEKG-GGKVTLVCLVSGFYPKDITVTWLKNGVPLTSGVSTSSPVEP-----NDGTYSVTSSLTVPPSDW-D 73

                          90
                  ....*....|....*..
gi 1859675635 226 PRNHFRCQVQFYGLSEN 242
Cdd:cd00098    74 EGATYTCVVTHESLKSP 90

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635 145 PEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEqpalNDSRYCLSSRLRVSATFWQ 224
Cdd:cd05768     1 PSVYLLPPPEEELSLNETVTLTCLVKGFYPEDIFVSWLQNGEPLPSADYKTTAPVPE----SDGSFFVYSKLNVSTADWN 76

                          90
                  ....*....|
gi 1859675635 225 NpRNHFRCQV 234
Cdd:cd05768    77 S-GDVFSCVV 85

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 1859675635 144 PPEVAVFEPSEAEIShTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPlkEQPalnDSRYCLSSRLRVSATFW 223
Cdd:cd07699     1 APSVTIFPPSSEELS-SGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTE--QQS---DNTYSMSSYLTLSSSDW 74

                          90
                  ....*....|....*..
gi 1859675635 224 qNPRNHFRCQVQFYGLS 240
Cdd:cd07699    75 -NKHKVYTCEVTHEGLS 90

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin E (IgE); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second constant domain of the heavy chain of immunoglobulin E (IgE). The basic structure of immunoglobulin (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). The different classes of antibodies vary in their heavy chains; the IgE class has the epsilon type. This domain (Cepsilon2) of IgE is in place of the flexible hinge region found in IgG.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635 145 PEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVH-SGVSTDPQplKEQpalnDSRYCLSSRLRVSATFW 223
Cdd:cd05847     1 PTVQILHSSCASTLTSETIQLLCLISGYTPSTIEVEWLVDGQVATlSAASTAPQ--KEE----GGTFSTTSKLNVTQEDW 74

                          90       100
                  ....*....|....*....|
gi 1859675635 224 QNPRNhFRCQVQFYGLSEND 243
Cdd:cd05847    75 KSGKT-YTCKVTHQGTTFEA 93

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of the major histocompatibility complex (MHC) class II alpha 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 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 1859675635 144 PPEVAVFEPSEAEIShtQKATLVCLATGFYPDHVELSWWVNGKEVHSGVS-TDPQPLKeqpalnDSRYCLSSRLrvsaTF 222
Cdd:cd05767     2 PPEVTVFPKSPVELG--EPNTLICFVDNFFPPVINVTWLRNGQPVTDGVSeTVFLPRE------DHSFRKFSYL----PF 69

                          90
                  ....*....|....*....
gi 1859675635 223 WQNPRNHFRCQVQFYGLSE 241
Cdd:cd05767    70 TPSEGDIYDCRVEHWGLEE 88

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 1859675635 144 PPEVAVFEPSEAEISHTQkatLVCLATGFYPDHVELSWWVNGKEVHSGVSTD---PQPlkeqpalnDSRYclssRLRVSA 220
Cdd:cd21029     2 KPRVRLSSRPSPGDGHLQ---LSCHVTGFYPRPIEVTWLRDGQEQMDGTQSGgilPNH--------DGTY----QLRKTL 66

                          90       100
                  ....*....|....*....|..
gi 1859675635 221 TFWQNPRNHFRCQVQFYGLSEN 242
Cdd:cd21029    67 DIAPGEGAGYSCRVDHSSLKQD 88

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) gamma chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the gamma chain of gamma/delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha/beta TCRs, but a small subset contain gamma/delta TCRs. Alpha/beta TCRs recognize antigens as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Gamma/delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds. The variable domain of gamma/delta TCRs is responsible for antigen recognition and is located at the N-terminus of the receptor. Members of this group contain the standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635  34 TGKKITLEC---SQTMGHDKMYWYQQDPGMEL-HLIHYSYGVNSTEKGDLSSESTVSR--IRTEHFPLTLESARPSHTSQ 107
Cdd:cd04982    12 ESKSVTISCkvsGIDFSTTYIHWYRQKPGQALeRLLYVSSTSAVRKDSGKTKNKFEARkdVGKSTSTLTITNLEKEDSAT 91

                          90       100
                  ....*....|....*....|....*...
gi 1859675635 108 YLCASSEARglaEFTDTQYFGPGTRLTV 135
Cdd:cd04982    92 YYCAYWESG---SGYYIKVFGSGTKLIV 116

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1859675635 144 PPEVAVFEPSEAEISHTQkaTLVCLATGFYPDHVELSWWVNGKEVHSGV-STDPQP 198
Cdd:cd05766     3 QPSVKVSPTKTGPLEHPN--LLVCSVTGFYPAEIEVKWFRNGQEETAGVvSTELIP 56

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
                  ....*....|....*....|....*....|....*....|....*...
gi 1859675635 145 PEVAVFEPSEAEISHTQkaTLVCLATGFYPDHVELSWWVNGKEVHSGV 192
Cdd:cd21000     4 PKVTVYPAKTQPLQHHN--LLVCSVNGFYPGSIEVRWFRNGQEEKAGV 49

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DQ and I-A; 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 human histocompatibility antigen (HLA) DQ and mouse I-A. 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). I-A and I-E have the same basic features insofar as peptide loading and presentation, they differ in that each interacts with distinctly different sets of peptides, and in the incidence of deletion of their genes. A structural understanding of the similarities and differences between I-A and I-E may help with understanding their roles in peptide presentation and T cell activation. Mouse I-Ag7 has a genetic susceptibility to autoimmune diabetes due to its small, uncharged amino acid residue at position 57 of their beta chain which results in the absence of a salt bridge between beta 57 and Arg alpha 76, which is adjacent to the P9 pocket of the peptide-binding groove. Human HLA-DR, -DQ, and -DP 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. HLA-DQ is involved in the autoimmune diseases celiac disease and diabetes mellitus type. DQ is one of several antigens involved in rejection of organ transplants. DQ2 is encoded by the HLA-DQB1*02 allele group. DQ6 is encoded by the HLA-DQB1*06 allele group. DQ2 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively. DQ6 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 alpha-chains. There are many haplotypes of DQ6. Susceptibility to Leptospirosis infection was found associated with undifferentiated DQ6. DQ8 is determined by the antibody recognition of beta8 and this generally detects the gene product of DQB1*0302. DQ8 is commonly linked to autoimmune disease in the human population. DQ8 is the second most predominant isoform linked to celiac disease and the DQ most linked to Type 1 diabetes. DQ8 increases the risk for rheumatoid arthritis and is linked to the primary risk locus for RA, HLA-DR4. DR4 also plays an important role in Type 1 diabetes. 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 response. They are expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice, and induced in nonprofessional APCs, such as keratinocyctes; they are expressed on the surface of activated human T cells and on T cells from other species. 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, and 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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1859675635 145 PEVAVFePSEAE-ISHTQkaTLVCLATGFYPDHVELSWWVNGKEVHSGVSTDP 196
Cdd:cd21001     4 PTVTIS-PSRTEaLNHHN--LLVCSVTDFYPGQIKVRWFRNDQEETAGVVSTP 53

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DM; 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) DM. Human HLA-DM plays a critical role in antigen presentation to CD4 T cells by catalyzing the exchange of peptides bound to MHC class II molecules. Type 1 diabetes is correlated with DM activation and it is also implicated in viral infections such as herpes simplex virus, celiac disease, multiple sclerosis, other autoimmune diseases, and leukemia. 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 1859675635 144 PPEVAVFEPseaEISHTQKAT-LVCLATGFYPDHVELSWWVNGKEV--HSGVSTDPQPlkeqpalN-DSRYCLSSRLRVS 219
Cdd:cd21002     3 PPSVRVAPT---TPFNTREPVmLACHVWGFYPADVTITWLKNGDPVapHSSAPKTAQP-------NgDWTYQTQVTLAVT 72

                          90       100
                  ....*....|....*....|..
gi 1859675635 220 ATFWQNprnhFRCQVQFYGLSE 241
Cdd:cd21002    73 PSPGDT----YTCSVQHASLPE 90

Immunoglobulin (Ig) variable (V) domain of Cluster of Differentiation (CD) 8 beta chain; The members here are composed of the immunoglobulin (Ig)-like domain in Cluster of Differentiation (CD) 8 beta. The CD8 glycoprotein plays an essential role in the control of T-cell selection, maturation, and the T-cell receptor (TCR)-mediated response to peptide antigen. CD8 is comprised of alpha and beta subunits and is expressed as either an alpha/alpha or alpha/beta dimer. Both dimeric isoforms can serve as a coreceptor for T cell activation and differentiation, however they have distinct physiological roles, different cellular distributions, unique binding partners, etc. Each CD8 subunit is comprised of an extracellular domain containing a V-type Ig-like domain, a single pass transmembrane portion, and a short intracellular domain. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635  25 QTPRYLVIGTGKKITLECSQ--TMGHDKMYWYQ--QDPGMELH---LIHYS------YGVN-STEKGDLSSESTVSRirt 90
Cdd:cd07700     3 QTPGSLLVQTNQTVKMSCEAktSPKNTRIYWLRqrQAPSKDSHfefLASWDpskgivYGEGvDQEKLIILSDSDSSR--- 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1859675635  91 ehFPLTLESARPSHTSQYLCAsseARGLAEFTdtqyFGPGTRLTV 135
Cdd:cd07700    80 --YILSLMSVKPEDSGTYFCM---TVGSPELI----FGTGTKLSV 115

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1859675635 144 PPEVAVFEPSEAEISHtqKATLVCLATGFYPDHVELSWWVNGKEVHSG-VSTDP 196
Cdd:cd21003     3 QPKVNVSPSKKGPLQH--HNLLVCHVTDFYPGNIQVRWFLNGQEETAGvVSTNL 54

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) delta chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the delta chain of gamma/delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha/beta TCRs, but a small subset contain gamma/delta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens; they recognize protein antigens directly and without antigen processing, and MHC independently of the bound peptide. Gamma/delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds. The variable domain of gamma/delta TCRs is responsible for antigen recognition and is located at the N-terminus of the receptor. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635  35 GKKITLECSQTMGHDKMY--WYQQDPGMEL-HLIHYSYGVNSTEKGDLSsestVSRIRTEH-FPLTLESARPSHTSQYLC 110
Cdd:cd07706    14 GEEVTLNCRYETSWTNYYlfWYKQLPSGEMtFLIRQDSSEQNAKSGRYS----VNFQKAQKsISLTISALQLEDSAKYFC 89

                          90       100
                  ....*....|....*....|....*
gi 1859675635 111 ASSEARGlaefTDTQYFGPGTRLTV 135
Cdd:cd07706    90 ALSLPYD----TDKLIFGKGTRLTV 110

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 1859675635 151 EPSEAEISHTQKA----TLVCLATGFYPDHVELSWWVNGKEvhsgVSTDPQPLKEQPAlNDSRYCLSSRLRVSATFWQNp 226
Cdd:cd21014     3 DPPKAHVTHHPRSygavTLRCWALGFYPADITLTWQLNGEE----LTQDMELVETRPA-GDGTFQKWASVVVPLGKEQN- 76

                          90
                  ....*....|....*
gi 1859675635 227 rnhFRCQVQFYGLSE 241
Cdd:cd21014    77 ---YTCHVNHEGLPE 88

Immunoglobulin constant (IgC)-like domain of antigen receptor Cluster of Differentiation (CD) 80; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin constant (IgC)-like domain of the antigen receptor Cluster of Differentiation (CD) 80. CD80 (also known as glycoprotein B7-1) and CD86 (also known as glycoprotein B7-2) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. CD80 contains two Ig-like domains, an amino-terminal immunoglobulin variable (IgV)-like domain characteristic of adhesion molecules, and a membrane proximal immunoglobulin constant (IgC)-like domain similar to the constant domains of antigen receptors. Members of the Ig 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 1859675635 143 FP-PEVAVFEPSEAEIShtqkaTLVCLATGFYPDHvELSWWVNGKE---VHSGVSTDPQplkeqpalnDSRYCLSSRLRV 218
Cdd:cd16083     1 FPvPSITEFGNPSPNIK-----RIICSTSGGFPEP-RLSWLENGEElnaINTTVSQDPE---------TELYTVSSELDF 65

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1859675635 219 SATfwqnpRNH-FRCQVQfYG---LSENDEW 245
Cdd:cd16083    66 NVT-----YNHsIVCLIK-YGdsrVSKNFTW 90

Class II major histocompatibility complex (MHC) beta 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 Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) I-E. 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). I-A and I-E molecules have the same basic features insofar as peptide loading and presentation, although each interacts with distinctly different sets of peptides. They also differ in that there is a relatively high incidence of deletion of the I-E gene in both inbred strains of mice as well as wild mice and the lack of the reverse situation i.e. the deletion of I-A genes. A detailed structural understanding of the similarities and differences between I-A and the paralogous I-E could help illuminate the respective roles these molecules play in peptide presentation and T cell activation. Mouse I-Ag7 has a genetic susceptibility to autoimmune diabetes due to its small, uncharged amino acid residue at position 57 of their beta chain which results in the absence of a salt bridge between beta 57 and Arg alpha 76, which is adjacent to the P9 pocket of the peptide-binding groove. 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
                  ....*....|....*....|....*....|....*....|....*...
gi 1859675635 145 PEVAVFEPSEAEISHTQkaTLVCLATGFYPDHVELSWWVNGKEVHSGV 192
Cdd:cd20998     7 PTVTVYPTKTQPLEHHN--LLVCSVSDFYPGNIEVRWFRNGKEEKTGI 52

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin delta 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 delta 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 1859675635 165 LVCLATGFYPDHVELSWWVngkevhsGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQnpRNHFRCQVQ 235
Cdd:cd16092    22 LACLITGYHPTSVTVTWYM-------GTQSQPQRTFPEIQRRDSYYMTSSQLSTPLQQWR--QGEYKCVVQ 83

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) E; 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) E. HLA-E is the first human class Ib major histocompatibility complex molecule to be crystallized. Like other MHC class I molecules, HLA-E is a heterodimer consisting of an a heavy chain and light chain beta-2-microglobulin. HLA-E is highly conserved and almost nonpolymorphic, and has recently been shown to be the first specialized ligand for natural killer cell receptors. 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 1859675635 150 FEPSEAEISH----TQKATLVCLATGFYPDHVELSWWVNGKevhsGVSTDPQPLKEQPAlNDSRYCLSSRLRVSAtfwqN 225
Cdd:cd21024     3 LEPPKTHVTHhpisDHEATLRCWALGFYPAEITLTWQQDGE----GHTQDTELVETRPA-GDGTFQKWAAVVVPS----G 73

                          90
                  ....*....|....*.
gi 1859675635 226 PRNHFRCQVQFYGLSE 241
Cdd:cd21024    74 EEQRYTCHVQHEGLPE 89

T cell receptor (TCR) gamma chain constant immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) constant (C) domain of the gamma chain of gamma-delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha-beta TCRs, but a small subset contain gamma-delta TCRs. Alpha-beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma-delta TCRs recognize intact protein antigens; they recognize protein antigens directly and without antigen processing and MHC independently of the bound peptide. Gamma-delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1859675635 145 PEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGvSTDPQPLKEqpalNDsRYCLSSRLRVSAtfwQ 224
Cdd:cd07697     2 PKPTIFLPSIAETEKQKAGTYLCLLENFFPDVIKIHWREKKSDTILE-SQEGNTEKT----KD-TYMKFSWLTVPK---K 72

                          90
                  ....*....|....*.
gi 1859675635 225 NPRNHFRCQVQFYGLS 240
Cdd:cd07697    73 SLGKEHRCIYKHENNK 88

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 1859675635 145 PEVAVFEpsEAEISHTQKATLVCLATGFYPDHVELSWWvngKEVHSGvsTDPQPLKEQPALN------DSRYCLSSRLRV 218
Cdd:cd05771     1 PRVRLSP--KNLVKPDLPQTLSCHIAGYYPLDVDVEWL---REEPGG--SESQVSRDGVSLSshrqsvDGTYSISSYLTL 73

                          90       100
                  ....*....|....*....|...
gi 1859675635 219 SATFWQNPRNhFRCQVQFYGLSE 241
Cdd:cd05771    74 EPGTENRGAT-YTCRVTHVSLEE 95

HLA class II histocompatibility antigen DO alpha; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the nonclassical MHC class II (MHCII) protein, HLA-DO, which binds HLA-DM and influences the repertoire of peptides presented by MHCII proteins. In complex with HLA-DM, HLA-DO adopts a classical MHCII structure, with alterations near the a subunit's 310 helix. HLA-DO binds to HLA-DM at the same sites implicated in MHCII interaction, and kinetic analysis showed that HLA-DO acts as a competitive inhibitor by acting as a substrate mimic. Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body namely, the exclusive expression of HLA-DO in B cells, thymic medullary epithelial cells, and dendritic cells indicate that it may be of physiological importance and has inspired further research. 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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1859675635 144 PPEVAVFEPSEAEIShtQKATLVCLATGFYPDHVELSWWVNGKEVHSGVS 193
Cdd:cd21004     2 PPRVTVLPKSRVELG--QPNILICIVDNIFPPVINITWLRNGQTVTEGVA 49