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 2024358113 154 APTITLFPPSKEELNeATKATLVCLINDFYPSPVTVDWVIDGSTRSG--ETTAPQRQSNSQYMASSYLSLSASDWSSHET 231
Cdd:cd07699     1 APSVTIFPPSSEELS-SGKATLVCLINKFYPGFATVTWKVDGSTVSSgvTTSKTEQQSDNTYSMSSYLTLSSSDWNKHKV 79

                          90       100
                  ....*....|....*....|
gi 2024358113 232 YTCRVTHNG--TSITKTLKR 249
Cdd:cd07699    80 YTCEVTHEGlsSTITKSFNR 99

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 2024358113 154 APTITLFPPSKEELNeATKATLVCLINDFYPSPVTVDWVIDGSTRSG--ETTAPQRQSNSQYMASSYLSLSASDWSSHET 231
Cdd:cd07699     1 APSVTIFPPSSEELS-SGKATLVCLINKFYPGFATVTWKVDGSTVSSgvTTSKTEQQSDNTYSMSSYLTLSSSDWNKHKV 79

                          90       100
                  ....*....|....*....|
gi 2024358113 232 YTCRVTHNG--TSITKTLKR 249
Cdd:cd07699    80 YTCEVTHEGlsSTITKSFNR 99

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024358113  172 KATLVCLINDFYPSPVTVDWVIDGS-TRSG-ETTAPQRQSNSQYMASSYLSLSASDWSSHETYTCRVTHNG 240
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQeVTEGvSTTDPLKNSDGTYFLSSYLTVPASTWESGDVYTCQVTHEG 71

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113   49 PTSVSANPGETVKITC--SGGIGQWYGWYQQKspgsvpvtvinantNRPSNIPSRFSGSESGSTATLTITGVRAEDEAVY 126
Cdd:smart00410   1 PPSVTVKEGESVTLSCeaSGSPPPEVTWYKQG--------------GKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTY 66

                           90       100
                   ....*....|....*....|.
gi 2024358113  127 YCgSADSSNTGIFGaGTTLTV 147
Cdd:smart00410  67 TC-AATNSSGSASS-GTTLTV 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 2024358113 154 APTITLFPPSKEELNeATKATLVCLINDFYPSPVTVDWVIDGSTRSG--ETTAPQRQSNSQYMASSYLSLSASDWSSHET 231
Cdd:cd07699     1 APSVTIFPPSSEELS-SGKATLVCLINKFYPGFATVTWKVDGSTVSSgvTTSKTEQQSDNTYSMSSYLTLSSSDWNKHKV 79

                          90       100
                  ....*....|....*....|
gi 2024358113 232 YTCRVTHNG--TSITKTLKR 249
Cdd:cd07699    80 YTCEVTHEGlsSTITKSFNR 99

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. 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. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113  46 LIQ-PTSVSANPGETVKITC--SGGIGQWY-GWYQQKsPGSVPVTVINANTNRPSN---IPSRFSGS-ESGSTATLTITG 117
Cdd:cd00099     1 VTQsPRSLSVQEGESVTLSCevSSSFSSTYiYWYRQK-PGQGPEFLIYLSSSKGKTkggVPGRFSGSrDGTSSFSLTISN 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2024358113 118 VRAEDEAVYYCGSADSSNTG--IFGAGTTLTV 147
Cdd:cd00099    80 LQPEDSGTYYCAVSESGGTDklTFGSGTRLTV 111

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024358113  172 KATLVCLINDFYPSPVTVDWVIDGS-TRSG-ETTAPQRQSNSQYMASSYLSLSASDWSSHETYTCRVTHNG 240
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQeVTEGvSTTDPLKNSDGTYFLSSYLTVPASTWESGDVYTCQVTHEG 71

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 2024358113 155 PTITLFPPSKEELNEATKATLVCLINDFYPSPVTVDWVIDG--STRSGETTAPQRQSNSQYMASSYLSLSASDWSSHETY 232
Cdd:cd05847     1 PTVQILHSSCASTLTSETIQLLCLISGYTPSTIEVEWLVDGqvATLSAASTAPQKEEGGTFSTTSKLNVTQEDWKSGKTY 80

                          90
                  ....*....|....*..
gi 2024358113 233 TCRVTHNGTSITKTLKR 249
Cdd:cd05847    81 TCKVTHQGTTFEAHTKK 97

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha 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 represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of 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 2024358113  49 PTSVSANPGETVKITCSGGIGQWYG--WYQQKsPGSVPVTVINANTNRPSNIPSRFS---GSESGSTaTLTITGVRAEDE 123
Cdd:cd04983     5 PQSLSVQEGENVTLNCNYSTSTFYYlfWYRQY-PGQGPQFLIYISSDSGNKKKGRFSatlDKSRKSS-SLHISAAQLSDS 82

                          90       100
                  ....*....|....*....|....*.
gi 2024358113 124 AVYYCGSADSSNTG--IFGAGTTLTV 147
Cdd:cd04983    83 AVYFCALSESGGTGklTFGKGTRLTV 108

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113   49 PTSVSANPGETVKITC--SGGIGQWYGWYQQKspgsvpvtvinantNRPSNIPSRFSGSESGSTATLTITGVRAEDEAVY 126
Cdd:smart00410   1 PPSVTVKEGESVTLSCeaSGSPPPEVTWYKQG--------------GKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTY 66

                           90       100
                   ....*....|....*....|.
gi 2024358113  127 YCgSADSSNTGIFGaGTTLTV 147
Cdd:smart00410  67 TC-AATNSSGSASS-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 2024358113  49 PTSVSANPGETVKITCSGGIG-QWYGWYQQkSPGSVP---VTVINANTNRPSNIP-SRFSGS-ESGSTATLTITGVRAED 122
Cdd:cd05899     5 PRYLIKRRGQSVTLRCSQKSGhDNMYWYRQ-DPGKGLqllFYSYGGGLNEEGDLPgDRFSASrPSLTRSSLTIKSAEPED 83

                          90       100
                  ....*....|....*....|....*..
gi 2024358113 123 EAVYYC--GSADSSNTGIFGAGTTLTV 147
Cdd:cd05899    84 SAVYLCasSLGGGADEAYFGPGTRLTV 110

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin mu chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin constant domain (IgC) of mu 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113 155 PTITLFPPSKEELNEATKATLVCLINDFYPSPVTVDWVIDG----STRSGETTAPQRQSNSQYMASSYLSLSASDWSSHE 230
Cdd:cd16093     2 PTVSLHAPSREEFLGNRTATFVCLATGFSPKTISFKWLRNGkevtSSTGAVVEEPKEDGKTLYSATSFLTITESEWKSQT 81

                          90
                  ....*....|....*...
gi 2024358113 231 TYTCRVTHNGTSITKTLK 248
Cdd:cd16093    82 EFTCEFKHKGEIVEKNAS 99

Immunoglobulin (Ig) heavy chain (H), variable (V) domain; The members here are composed of the immunoglobulin (Ig) heavy chain (H), variable (V) domain. This group contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology. 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 determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which can associate with any of the heavy chains. This family includes alpha, gamma, delta, epsilon, and mu heavy chains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113  45 ELIQPTSVSANPGETVKITC--SGGI--GQWYGWYQQkSPGSVP-----VTVINANTNRPSNIPSRFSGSE--SGSTATL 113
Cdd:cd04981     1 QLQESGPGLVKPGQSLKLSCkaSGFTftSYGMGWVRQ-APGKGLewiglIYPGGGDTYYADSFKGRFTITRdtSKSTAYL 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2024358113 114 TITGVRAEDEAVYYC----GSADSSNTGIFGAGTTLTV 147
Cdd:cd04981    80 QLNSLTSEDTAVYYCarglGGYGYSYFDYWGQGTTVTV 117

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 2024358113  50 TSVSANPGETVKITCSGGIGQWYG---WYQQKSPGSVpVTVINANTNRPSNIPSRFSGS--ESGSTATLTITGVRAEDEA 124
Cdd:cd07706     7 PDVSVQVGEEVTLNCRYETSWTNYylfWYKQLPSGEM-TFLIRQDSSEQNAKSGRYSVNfqKAQKSISLTISALQLEDSA 85

                          90       100
                  ....*....|....*....|....*
gi 2024358113 125 VYYCGSADSSNTG--IFGAGTTLTV 147
Cdd:cd07706    86 KYFCALSLPYDTDklIFGKGTRLTV 110

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, delta, epsilon, gamma, and mu chains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113 154 APTITLFPPSkEELNEATKATLVCLINDFYPSPVTVDW------VIDGSTRsgeTTAPQRQSNSQYMASSYLSLSASDWS 227
Cdd:cd04985     1 APTVFPLQSA-TKSQSNGPVALGCLISDYFPESITVSWqkntnsITSGFTR---TFPVVLRSGGDYSCSSQLTVPLQEWN 76

                          90       100
                  ....*....|....*....|..
gi 2024358113 228 SHETYTCRVTHNGTSITKTLKR 249
Cdd:cd04985    77 SGEVYKCQVQHSASNSKQEKDV 98

Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins. pIgR delivers dimeric IgA and pentameric IgM to mucosal secretions. Polymeric immunoglobulin (pIgs) are the first defense against pathogens and toxins. IgA and IgM can form polymers via an 18-residue extension at their C-termini referred to as the tailpiece. pIgR transports pIgs across mucosal epithelia into mucosal secretions. Human pIgR is a glycosylated type I transmembrane protein, comprised of a 620-residue extracellular region, a 23-residue transmembrane region, and a 103-residue cytoplasmic tail. The extracellular region contains five domains that share sequence similarity with Ig variable (v) regions. This group also contains the Ig-like extracellular domains of other receptors such as NK cell receptor Nkp44 and myeloid receptors, among others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113  48 QPTSVSANPGETVKITCSggIGQWYGWYQ---QKSPGSVPVTVInanTNRPSNIPSRFSGSESG--STATLTITGVRAED 122
Cdd:cd05716     3 GPEVVTGVEGGSVTIQCP--YPPKYASSRkywCKWGSEGCQTLV---SSEGVVPGGRISLTDDPdnGVFTVTLNQLRKED 77

                          90
                  ....*....|....*..
gi 2024358113 123 EAVYYCGSADSSNTGIF 139
Cdd:cd05716    78 AGWYWCGVGDDGDRGLT 94

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy alpha 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 alpha chains. It belongs to a family composed of the first immunoglobulin constant-1 set domain of alpha, 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113 158 TLFPPSKEELNEATKATLVCLINDFYPSPVTVDWVIDGSTRSGETTAPQRQSNSQYMASSYLSLSASDWSSHETYTCRVT 237
Cdd:cd21818     3 TVFPLSLCPSLSSDPVVIGCLVQGFFPEPVNVTWNYSGKGGTARNFPAMLASGGRYTQSSQLTLPADQCPEGEAYKCSVQ 82

                          90
                  ....*....|
gi 2024358113 238 HNGTSITKTL 247
Cdd:cd21818    83 HYSPSQDLNV 92

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113 152 KVAPTITLFPPSKEELNEATkaTLVCLINDFYPSPVTVDWVIDGSTRSGETTAPQRQSNSQYMASSYLSLSASDwSSHET 231
Cdd:cd20998     4 RVEPTVTVYPTKTQPLEHHN--LLVCSVSDFYPGNIEVRWFRNGKEEKTGIVSTGLVRNGDWTFQTLVMLETVP-QSGEV 80

                  ....*..
gi 2024358113 232 YTCRVTH 238
Cdd:cd20998    81 YTCQVEH 87

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 2024358113 155 PTITLFPpsKEELNEATKATLVCLINDFYPSPVTVDWVIDGSTRSGETTA--------PQRQSNSQYMASSYLSLSASDW 226
Cdd:cd05771     1 PRVRLSP--KNLVKPDLPQTLSCHIAGYYPLDVDVEWLREEPGGSESQVSrdgvslssHRQSVDGTYSISSYLTLEPGTE 78

                          90
                  ....*....|..
gi 2024358113 227 SSHETYTCRVTH 238
Cdd:cd05771    79 NRGATYTCRVTH 90

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 2024358113 174 TLVCLINDFYPSPVTVDWVIDGSTR-SGETTAPQRQSNSQYMASSYLSLSASDWSSHETYTCRVTHNGTSITKTLK 248
Cdd:cd21819    19 TVGCLATDFLPDSITFSWTDDNNSLtTGVKTYPSVLTGGTYTASSQLQVPESEWKSKENFYCKVEHPGGNKEVPVP 94

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 2024358113 152 KVAPTITLFPPSKEELNEATkaTLVCLINDFYPSPVTVDWVIDGSTRSGETTAPQRQSNSQYMASSYLSLSASDWSShET 231
Cdd:cd21000     1 RVEPKVTVYPAKTQPLQHHN--LLVCSVNGFYPGSIEVRWFRNGQEEKAGVVSTGLIQNGDWTFQTLVMLETVPRSG-EV 77

                  ....*..
gi 2024358113 232 YTCRVTH 238
Cdd:cd21000    78 YTCQVEH 84

T-cell receptor Mu, Heavy chain, variable (V) domain; The members here are composed of the immunoglobulin (Ig) heavy chain (H), variable (V) domain of the T-cell receptor Mu. 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 determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which can associate with any of the heavy chains. This family includes alpha, gamma, delta, epsilon, and mu heavy chains. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113  57 GETVKITCSGGIGQ-------WYGWyqqkSPGSVP--VTVINANTNRPSNIPSRFSGSESGSTATLTITGVRAEDEAVYY 127
Cdd:cd16095    15 GKTLSLKCQTSGFQfntsqlsWYLW----VPGHAPlwLTSLDHISTKVSEDRITSSREDTNSQIFLQIKGLGLRDSGQYH 90

                          90       100
                  ....*....|....*....|....
gi 2024358113 128 C----GSADSSNTGIFGAGTTLTV 147
Cdd:cd16095    91 CarrvGYGDDTDKLIFGPGTDVIV 114

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 2024358113  46 LIQ-PTSVSANPGETVKITC-------SGGIgQWYGWYQQKSPGS----------VPVTVINANTNRPSNIPSRFSgseS 107
Cdd:cd07700     1 LLQtPGSLLVQTNQTVKMSCeaktspkNTRI-YWLRQRQAPSKDShfeflaswdpSKGIVYGEGVDQEKLIILSDS---D 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2024358113 108 GSTATLTITGVRAEDEAVYYCGSADSSNTgIFGAGTTLTV 147
Cdd:cd07700    77 SSRYILSLMSVKPEDSGTYFCMTVGSPEL-IFGTGTKLSV 115

Class I major histocompatibility complex (MHC) beta-2-microglobulin; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in beta-2-microglobulin (beta2m). Beta2m is the non-covalently bound light chain of the human class I major histocompatibility complex (MHC-I). Beta2m is structured as a beta-sandwich domain composed of two facing beta-sheets (four stranded and three stranded), that is typical of the C-type immunoglobulin superfamily. This structure is stabilized by an intramolecular disulfide bridge connecting two Cys residues in the facing beta-sheets. In vivo, MHC-I continuously exposes beta2m on the cell surface, where it may be released to plasmatic fluids, transported to the kidneys, degraded, and finally excreted.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024358113 151 PKVApTITLFPPSkeelnEATKATLVCLINDFYPSPVTVDWVIDGSTRSG-ETTAPQRQSNSQYMASSYLSLSAsdwSSH 229
Cdd:cd05770     3 PKVQ-VYSRFPAE-----NGKPNVLNCYVSGFHPPDIEIRLLKNGVKIEDvEQSDLSFSKDWTFYLLKYTEFTP---TKG 73

                          90
                  ....*....|....*....
gi 2024358113 230 ETYTCRVTHNGTSITKTLK 248
Cdd:cd05770    74 DEYACRVRHNTLSEPKIYK 92