HLA-A gene

major histocompatibility complex, class I, A

The information on this page was automatically extracted from online scientific databases.

From NCBI Gene:

HLA-A belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-A alleles have been described. [provided by RefSeq, Jul 2008]

From UniProt: 1A01_HUMAN:

Antigen-presenting major histocompatibility complex class I (MHCI) molecule, HLA-A*01 serotype. 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-A*01-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:1402688, PubMed:7504010, PubMed:17189421, PubMed:19177349, PubMed:26758806, PubMed:24395804). May also present self-peptides, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:25880248, PubMed:7506728). 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. Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome or via endopeptidase IDE/insulin-degrading enzyme (PubMed:17189421, PubMed:20364150). Can bind different peptides that share a common structural motif defined by the nature of the peptide anchor residues. HLA-A*01:01 presents a restricted peptide repertoire including viral epitopes derived from IAV NP/nucleoprotein (CTELKLSDY), IAV PB1/polymerase basic protein 1 (VSDGGPNLY), HAdV-11 capsid L3/hexon protein (LTDLGQNLLY) as well as tumor peptide antigens including MAGE1 (EADPTGHSY), MAGEA3 (EVDPIGHLY) and WT1 (TSEKRPFMCAY), all having in common a canonical motif with a negatively charged Asp or Glu residue at position 3 and a Tyr anchor residue at C-terminal (PubMed:1402688, PubMed:7504010, PubMed:17189421, PubMed:20364150, PubMed:25880248, PubMed:30530481, PubMed:24395804, PubMed:26758806). A number of HLA-A*01:01-restricted peptides carry a post-translational modification with oxidation and N-terminal acetylation being the most frequent (PubMed:25880248). Fails to present highly immunogenic peptides from the EBV latent antigens (PubMed:18779413).

From UniProt: 1A03_HUMAN:

Antigen-presenting major histocompatibility complex class I (MHCI) molecule, HLA-A*03 serotype. 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-A*03-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:2456340, PubMed:7504010, PubMed:7679507, PubMed:9862734, PubMed:19543285, PubMed:21943705). 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:7679507). 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. Typically presents intracellular peptide antigens of 8 to 11 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome (PubMed:27049119). Can bind different peptides that share a common structural motif defined by the nature of the peptide anchor residues. HLA-A*03:01 presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK) as well tumor peptide antigens including PMEL (LIYRRRLMK), NODAL (HAYIQSLLK), TRP-2 (RMYNMVPFF), all having in common hydrophobic amino acids at position 2 and LYS or ARG anchor residues at C-terminal (PubMed:7504010, PubMed:7679507, PubMed:9862734, PubMed:19543285, PubMed:21943705). May also display spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119).

Covered on Genetics Home Reference:

From NCBI Gene:

  • Susceptibility to severe cutaneous adverse reaction

From UniProt: 1A03_HUMAN:

HLA-A*03:01 allele increases the susceptibility to multiple sclerosis (MS), an autoimmune disease of the central nervous system (PubMed:10746785). Proposed to contribute to the initiation phase of the disease by presenting myelin PLP1 self-peptide (KLIETYFSK) to autoreactive CD8-positive T cells capable of initiating the first autoimmune attacks (PubMed:18953350).

Cytogenetic Location: 6p22.1, which is the short (p) arm of chromosome 6 at position 22.1

Molecular Location: base pairs 29,942,532 to 29,945,870 on chromosome 6 (Homo sapiens Updated Annotation Release 109.20190607, GRCh38.p13) (NCBI)

Cytogenetic Location: 6p22.1, which is the short (p) arm of chromosome 6 at position 22.1