HLA-B (HLA class I histocompatibility antigen, B alpha chain)

FEATURES

DESCRIPTION

Also known as HLAB_HUMAN, HLA-B, HLAB. Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-B-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:25808313, PubMed:29531227, PubMed:9620674, PubMed:23209413). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:7743181, PubMed:18991276). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:29531227, PubMed:9620674, PubMed:24600035). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via constitutive proteasome and IFNG-induced immunoproteasome (PubMed:23209413). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:25808313, PubMed:29531227)., Allele B*07:02: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and mainly a Leu anchor residue at the C-terminus (PubMed:7743181). Presents a long peptide (APRGPHGGAASGL) derived from the cancer-testis antigen CTAG1A/NY-ESO-1, eliciting a polyclonal CD8-positive T cell response against tumor cells (PubMed:29531227). Presents viral epitopes derived from HIV-1 gag-pol (TPQDLNTML) and Nef (RPQVPLRPM) (PubMed:25808313). Displays self-peptides including a peptide derived from the signal sequence of HLA-DPB1 (APRTVALTA) (PubMed:7743181)., Allele B*08:01: Presents to CD8-positive T cells viral epitopes derived from EBV/HHV-4 EBNA3 (QAKWRLQTL), eliciting cytotoxic T cell response., Allele B*13:02: Presents multiple HIV-1 epitopes derived from gag (RQANFLGKI, GQMREPRGSDI), nef (RQDILDLWI), gag-pol (RQYDQILIE, GQGQWTYQI) and rev (LQLPPLERL), all having in common a Gln residue at position 2 and mainly hydrophobic amino acids Leu, Ile or Val at the C-terminus. Associated with succesful control of HIV-1 infection., Allele B*18:01: Preferentially presents octomeric and nonameric peptides sharing a common motif, namely a Glu at position 2 and Phe or Tyr anchor residues at the C-terminus (PubMed:14978097, PubMed:23749632, PubMed:18991276). Presents an EBV/HHV-4 epitope derived from BZLF1 (SELEIKRY) (PubMed:23749632). May present to CD8-positive T cells an antigenic peptide derived from MAGEA3 (MEVDPIGHLY), triggering an anti-tumor immune response (PubMed:12366779). May display a broad repertoire of self-peptides with a preference for peptides derived from RNA-binding proteins (PubMed:14978097)., Allele B*27:05: Presents to CD8-positive T cells immunodominant viral epitopes derived from HCV POLG (ARMILMTHF), HIV-1 gag (KRWIILGLNK), IAV NP (SRYWAIRTR), EBV/HHV-4 EBNA4 (HRCQAIRKK) and EBV/HHV-4 EBNA6 (RRIYDLIEL), confering longterm protection against viral infection (PubMed:19139562, PubMed:18385228, PubMed:15113903, PubMed:9620674). Can present self-peptides derived from cytosolic and nuclear proteins. All peptides carry an Arg at position 2 (PubMed:1922338). The peptide-bound form interacts with NK cell inhibitory receptor KIR3DL1 and inhibits NK cell activation in a peptide-specific way, being particularly sensitive to the nature of the amino acid side chain at position 8 of the antigenic peptide (PubMed:8879234, PubMed:15657948). KIR3DL1 fails to recognize HLA-B*27:05 in complex with B2M and EBV/HHV-4 EBNA6 (RRIYDLIEL) peptide, which can lead to increased activation of NK cells during infection (PubMed:15657948). May present an altered repertoire of peptides in the absence of TAP1-TAP2 and TAPBPL (PubMed:9620674)., Allele B*40:01: Pres Heterotrimer that consists of an alpha chain HLA-B, a beta chain B2M and a peptide (peptide-HLA-B-B2M) (PubMed:25808313, PubMed:29531227, PubMed:15657948, PubMed:17057332, PubMed:22020283, PubMed:24600035). Early in biogenesis, HLA-B-B2M dimer interacts with the components of the peptide-loading complex composed of TAPBP, TAP1-TAP2, TAPBPL, PDIA3/ERP57 and CALR (PubMed:9036970, PubMed:9620674, PubMed:26439010, PubMed:26416272). Interacts with TAP1-TAP2 transporter via TAPBP; this interaction is obligatory for the loading of peptide epitopes delivered to the ER by TAP1-TAP2 transporter (PubMed:9036970, PubMed:9620674). Interacts with TAPBPL; TAPBPL binds peptide-free HLA-B-B2M complexes or those loaded with low affinity peptides, likely facilitating peptide exchange for higher affinity peptides (PubMed:26439010). Only optimally assembled peptide-HLA-B-B2M trimer translocates to the surface of antigen-presenting cells, where it interacts with TCR and CD8 coreceptor on the surface of T cells. HLA-B (via polymorphic alpha-1 and alpha-2 domains) interacts with antigen-specific TCR (via CDR1, CDR2 and CDR3 domains) (PubMed:29531227, PubMed:24600035). One HLA-B molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop); this interaction insures peptide-HLA-B-B2M recognition by CD8-positive T cells only (PubMed:29531227). Allele B*57:01 interacts (via Bw4 motif) with KIR3DL1 (via Ig-like C2-type domain); this interaction may interfere with peptide binding (PubMed:22020283, PubMed:25480565). Allele B*46:01 interacts with KIR2DL3 (PubMed:28514659).

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EXTERNAL LINKS

HLA-B

HLA class I histocompatibility antigen, B alpha chain

MOLECULAR SYNOPSIS STRUCTURAL LIGANDABILITY

HLA-B

Molecular Synopsis