Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229577039   24 PDKPVQALVGEDAAFSCFLSPKTNAEAMEVRFFR---GQFSSVVHLYRDGKDQPFMQMPQYQGRtklvkDSIAEGRISLR 100
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEASTSVYWYRqppGKGPTFLIAYYSNGSEEGVKKGRFSGR-----GDPSNGDGSLT 76

                          90       100
                  ....*....|....*....|.
gi 229577039  101 LENITVLDAGLYGCRISSQSY 121
Cdd:pfam07686  77 IQNLTLSDSGTYTCAVIPSGE 97

Immunoglobulin Variable (IgV) domain of B7-H4; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H4 (also known as B7-S1, B7x, or Vtcn1). B7-H4 is one of the B7 family of immune-regulatory ligands that act as negative regulators of T cell function; it contains one IgV domain and one IgC domain. The B7-family consists of structurally related cell-surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. The binding of B7-H4 to unidentified receptors results in the inhibition of TCR-mediated T cell proliferation, cell-cycle progression and IL-2 production. As a co-inhibitory molecule, B7-H4 is widely expressed in tumor tissues and its expression is significantly associated with poor prognosis in human cancers such as glioma, pancreatic cancer, oral squamous cell carcinoma, renal cell carcinoma, and lung cancer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229577039  30 ALVGEDAAFSCFLSPKTNAEAMEVRFFRGQFSSVVHLYRDGKDQPFMQMPQYQGRTKLVKDSIAEGRISLRLENITVLDA 109
Cdd:cd20984    9 GNIGEDGILSCTFTPDIKLSDIVIQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQLTDA 88

                 ....*....
gi 229577039 110 GLYGCRISS 118
Cdd:cd20984   89 GTYLCIISN 97

Immunoglobulin Variable (IgV) domain of B7-H3, a member of the B7 family of immune checkpoint molecules; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H3 also known as CD276), a member of the B7 family of immune checkpoint molecules. B7-H3 is an important immune checkpoint member of the B7 family and shares homology with other B7 ligands such as programmed death ligand 1 (PD-L1). The B7 family molecules interact with CD28 on T-cells to provide co-stimulatory signals that regulate T-cell activation and T-helper cell differentiation. Although B7-H3 has been shown to have both co-stimulatory and co-inhibitory effects on T-cell responses, the most current studies describe B7-H3 as a T cell inhibitor that promotes tumor aggressiveness and proliferation. Moreover, B7-H3 is highly overexpressed on a wide range of human solid cancers and promotes tumor growth, metastasis, and drug resistance. Thus, B7-H3 expression in tumors often correlates with both negative prognosis and poor clinical outcome in cancer patients. B7-H3 protein contains a predicted signal peptide, V- and C-like Ig domains (IgV and IgC), a transmembrane region, and an intracellular tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229577039  24 PDKPVQALVGEDAAFSCFLSPKTNAEAMEVRFFrGQFSS---VVHLYRDGKDQPFMQMPQYQGRTKLVKDSIAEGRISLR 100
Cdd:cd20934    3 PEDPVVALVGTDATLRCSFSPEPGFSLAQLSVF-WQLTDtkqLVHSFTESQDQGRDQGSAYANRTALFPDLLAQGNASLR 81

                         90       100       110
                 ....*....|....*....|....*....|...
gi 229577039 101 LENITVLDAGLYGCRISSQSYYQKAIwELQVSA 133
Cdd:cd20934   82 LQRVRVADEGSYTCFVSVQDFGSAAV-SLQVAA 113

Immunoglobulin Variable (IgV) domain of T cell Immunoglobulin Domain and Mucin Domain 3 (Tim-3), and similar domains; The members here are composed of the immunoglobulin variable (IgV) domain of T cell immunoglobulin domain and mucin domain 3 (Tim-3; also known as Hepatitis A virus cellular receptor 2 (HAVcr-2) and Cluster of Differentiation 366 (CD366)) and similar proteins. TIM-3 is a checkpoint inhibitor in immune responses to tumors, as well as involved in chronic viral infections. Thus, Tim-3 has emerged as one of most promising immune checkpoint targets for cancer immunotherapy. Tim-3 is highly expressed on Th1 lymphocytes and CD11b(+) macrophages and is upregulated on activated T and myeloid cells. TIM-3 regulates macrophage, activation and inhibits Th1 mediated immune responses to promote immunological tolerance. There are three TIM family members in humans (TIM-1, TIM-3, and TIM-4) and eight members in mice (TIM-1 to TIM-8). The IgV domain of human TIM-3 has been shown to bind ligands such as carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), high mobility group protein B1 (HMGB1)and galectin-9 (GAL9). The binding of GAL9 to TIM-3 can negatively regulate Th1 immune response, enhance immune tolerance and inhibit anti#tumor immunity. Dysregulation of the TIM-3/GAL9 pathway is implicated in numerous chronic autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229577039  28 VQALVGEDAAFSCFLSPKTNAEAMEVRFFRGQFSSV----VHLYRDGKDQPFMQMPQYQgrtklVKDSIAEGRISLRLEN 103
Cdd:cd20982    3 YRAEVGHNAYLPCSYTTAAPGNLVPVCWGKGACPVSycgnVLLRTDERDVTYQKSSRYQ-----LKGDFSKGDVSLTIEN 77

                         90
                 ....*....|...
gi 229577039 104 ITVLDAGLYGCRI 116
Cdd:cd20982   78 VTLADSGIYCCRI 90

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 86; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 86). Glycoproteins B7-1 (also known as cluster of differentiation (CD) 80) and B7-2 (also known as CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (also known as CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. The CTLA-4 and B7-2 monomers are both two-layer beta-sandwiches that display the chain topology characteristic of the immunoglobulin variable (V-type) domains present in antigen receptors. The front and back sheets of B7-2 are composed of AGFCC'C" and BED strands, respectively. Members of the IgV family 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229577039  28 VQALVGEDAAFSCflsPKTNAEAME----VRFFRGQFSSVVH-LYRdGKDQPFMQMPQYQGRTKLVKDSIAegrisLRLE 102
Cdd:cd16087    3 IQAYFNETAYLPC---QFKNPQNISlselVVFWQDQKKLVLYeLYL-GKEKLDNVNSKYIGRTSFDQENWT-----LQLH 73

                         90
                 ....*....|....
gi 229577039 103 NITVLDAGLYGCRI 116
Cdd:cd16087   74 NVQIKDQGTYQCFI 87

Immunoglobulin Variable (IgV) domain of B7-H2 (B7 homolog 2); The members here are composed of the immunoglobulin variable (IgV) domain of B7-H2 (B7 homolog 2 also known as ICOSL (inducible T cell costimulator ligand) or CD275). B7-H2 is a ligand for the T-cell-specific cell surface receptor ICOS and acts as a costimulatory signal for T-cell proliferation and cytokine secretion. The interaction of ICOS with ICOSL (B7-H2) regulates T cell activation and expansion, is involved in T cell dependent B cell activation, and T-helper cell differentiation. It is a member of the B7 family of immune regulatory proteins and shares homology with other B7 ligands, such as B7-1, B7-2, B7-H1 (PD-L1), PD-L2, and B7-H3. The extracellular domains of B7 proteins contain two Ig-like domains and all members have short cytoplasmic domains. These ligands are typically expressed on antigen presenting cells (such as macrophages, B cells and dendritic cells) and have the ability to regulate T-cell proliferation and function. Tumor cells are also capable of expressing the B7 family members in order to evade immune surveillance.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229577039  26 KPVQALVGEDAAFSCfLSPKTNAEAMEVRFFRGQFS---SVVHLYRDGKDQPFMQMPQYQGRTKLVKDSIAEGRISLRLE 102
Cdd:cd20935    1 KEVRAMVGSDVELSC-ICPEGSRFDLNDLYVYWQISeseTVVTYHLPQNSSLENVDSHYRNRALLSLDSMKQGDFSLRLF 79

                         90       100
                 ....*....|....*....|....*....
gi 229577039 103 NITVLDAGLYGCRISSQSYYQKAIWELQV 131
Cdd:cd20935   80 NVTPQDEQKFHCLVFSQSLELQKVLEVVV 108