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HLA-A

GeneName

HLA-A

Summary

HLA-A, also referred to as HLA class I or HLA A2, is a 41 kDa glycoprotein that is a crucial component of the major histocompatibility complex (MHC) class I molecules. It is predominantly expressed on the surface of nucleated cells and plays a vital role in the immune system by presenting endogenous peptide antigens to CD8+ T cells. HLA-A is localised to various cellular compartments, including the endoplasmic reticulum, Golgi apparatus, and plasma membrane, and is involved in processes such as antigen processing and presentation. It interacts with beta-2-microglobulin and is essential for T cell receptor binding, facilitating T cell activation and immune responses against pathogens.

Importance

HLA-A is relevant to: - The immune response to viral infections and cancer due to its role in presenting antigens to CD8+ T cells. - Transplantation biology as it is a key factor in graft rejection and compatibility. - Autoimmune diseases where HLA-A may influence susceptibility and disease progression. - Vaccine development, particularly in designing vaccines that elicit strong CD8+ T cell responses.

Top Products

For researchers investigating HLA-A, we highly recommend the top-selling recombinant antibody, Anti-HLA A antibody [EP1395Y] (ab52922). This antibody has been validated in knockout models, ensuring its reliability in various applications, including flow cytometry (FC), immunohistochemistry (IHC), western blotting (WB), immunocytochemistry (ICC), and immunoprecipitation (IP). With 115 citations, it is well-regarded in the research community, making it an excellent choice for those seeking dependable detection of HLA-A.

Abcam Product Citation Summary

The use of the Abcam antibody ab52922 for HLA-A detection highlights its role as a loading control in Western blotting, specifically in human samples. This suggests its importance in studies involving protein expression analysis.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab52922
Human
WB
28680364

Domain

The alpha-1 domain is a structural part of the peptide-binding cleft.

The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:19177349, PubMed:19542454, PubMed:20619457, PubMed:20844028, PubMed:21543847, PubMed:21943705, PubMed:22245737, PubMed:24395804, PubMed:26758806, PubMed:2784196, PubMed:28250417, PubMed:7694806, PubMed:8906788). Mediates the interaction with TAP1-TAP2 complex (PubMed:8805302).

The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor.

The VL9 peptide/epitope (VMAPRT[V/L][L/V/I/F]L) derived from the signal sequence is loaded onto HLA-E and enables HLA-E expression at the plasma membrane. Distinct VL9 peptides presented by HLA-E variably affect its recognition by KLRD1-KLRC1 or KLRD1-KLRC2 receptors on NK cells, setting NK cell activation threshold. Common HLA-A allotypes contain functional VL9 peptides (VMAPRTLLL, VMAPRTLVL and VPAPRTLLL).

Function

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-A-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:10449296, PubMed:12138174, PubMed:12393434, PubMed:1402688, PubMed:15893615, PubMed:17189421, PubMed:19543285, PubMed:21498667, PubMed:24192765, PubMed:24395804, PubMed:2456340, PubMed:2784196, PubMed:28250417, PubMed:7504010, PubMed:7694806, PubMed:9862734). 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:25880248, PubMed:7506728, 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 (PubMed:12796775, PubMed:18275829, PubMed:19542454, PubMed:28250417). 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:17079320, PubMed:17189421, PubMed:20364150, PubMed:26929325, PubMed:27049119). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:7504010, PubMed:9862734).

Allele 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), SARS-CoV-2 3a/ORF3a (FTSDYYQLY) 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 the C-terminus (PubMed:1402688, PubMed:17189421, PubMed:19177349, PubMed:20364150, PubMed:24395804, PubMed:25880248, PubMed:26758806, PubMed:30530481, PubMed:32887977, PubMed:7504010). 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).

Allele A*02:01: A major allele in human populations, presents immunodominant viral epitopes derived from IAV M/matrix protein 1 (GILGFVFTL), HIV-1 env (TLTSCNTSV), HIV-1 gag-pol (ILKEPVHGV), HTLV-1 Tax (LLFGYPVYV), HBV C/core antigen (FLPSDFFPS), HCMV UL83/pp65 (NLVPMVATV) as well as tumor peptide antigens including MAGEA4 (GVYDGREHTV), WT1 (RMFPNAPYL) and CTAG1A/NY-ESO-1 (SLLMWITQC), all having in common hydrophobic amino acids at position 2 and at the C-terminal anchors.

Allele A*03:01: Presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK), SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) as well as 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 the C-terminus (PubMed:19543285, PubMed:21943705, PubMed:2456340, PubMed:32887977, PubMed:7504010, PubMed:7679507, PubMed:9862734). 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).

Allele A*11:01: Presents several immunodominant epitopes derived from HIV-1 gag-pol and HHV-4 EBNA4, containing the peptide motif with Val, Ile, Thr, Leu, Tyr or Phe at position 2 and Lys anchor residue at the C-terminus. Important in the control of HIV-1, EBV and HBV infections (PubMed:10449296). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) (PubMed:32887977).

Allele A*23:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.

Allele A*24:02: Presents viral epitopes derived from HIV-1 nef (RYPLTFGWCF), EBV lytic- and latent-cycle antigens BRLF1 (TYPVLEEMF), BMLF1 (DYNFVKQLF) and LMP2 (IYVLVMLVL), SARS-CoV nucleocapsid/N (QFKDNVILL), as well as tumor peptide antigens including PRAME (LYVDSLFFL), all sharing a common signature motif, namely an aromatic residue Tyr or Phe at position 2 and a nonhydrophobic anchor residue Phe, Leu or Iso at the C-terminus (PubMed:12393434, PubMed:20844028, PubMed:24192765, PubMed:9047241). Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response (PubMed:17182537, PubMed:18502829).

Allele A*26:01: Presents several epitopes derived from HIV-1 gag-pol (EVIPMFSAL, ETKLGKAGY) and env (LVSDGGPNLY), carrying as anchor residues preferentially Glu at position 1, Val or Thr at position 2 and Tyr at the C-terminus.

Allele A*29:02: Presents peptides having a common motif, namely a Glu residue at position 2 and Tyr or Leu anchor residues at the C-terminus.

Allele A*32:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.

Allele A*68:01: Presents viral epitopes derived from IAV NP (KTGGPIYKR) and HIV-1 tat (ITKGLGISYGR), having a common signature motif namely, Val or Thr at position 2 and positively charged residues Arg or Lys at the C-terminal anchor.

Allele A*74:01: Presents immunodominant HIV-1 epitopes derived from gag-pol (GQMVHQAISPR, QIYPGIKVR) and rev (RQIHSISER), carrying an aliphatic residue at position 2 and Arg anchor residue at the C-terminus. May contribute to viral load control in chronic HIV-1 infection.

Involvement in disease

Alleles A*02:01 and A*24:02 are associated with increased susceptibility to diabetes mellitus, insulin-dependent (IDDM) (PubMed:16731854, PubMed:18802479, PubMed:22245737, PubMed:22522618). In a glucose-dependent way, allele A*02:01 may aberrantly present the signal peptide of preproinsulin (ALWGPDPAAA) on the surface of pancreatic beta cells to autoreactive CD8-positive T cells, potentially driving T-cell mediated cytotoxicity in pancreatic islets (PubMed:18802479, PubMed:22245737). Allele A*24:02 may present the signal peptide of preproinsulin (LWMRLLPLL) and contribute to acute pancreatic beta-cell destruction and early onset of IDDM (PubMed:16731854, PubMed:22522618).

Allele A*03:01 is associated with increased susceptibility to multiple sclerosis (MS), an autoimmune disease of the central nervous system (PubMed:10746785). May 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).

Allele A*26:01 is associated with increased susceptibility to Behcet disease (BD) in the Northeast Asian population. Especially in the HLA-B*51-negative BD populations, HLA-A*26 is significantly associated with the onset of BD.

Allele A*29:02 is associated with increased susceptibility to birdshot chorioretinopathy (BSCR). May aberrantly present retinal autoantigens and induce autoimmune uveitis.

Post-translational modifications

(Microbial infection) Polyubiquitinated in a post ER compartment by interaction with human herpesvirus 8 MIR1 protein. This targets the protein for rapid degradation via the ubiquitin system.

N-linked glycosylation at Asn-110.

Sequence Similarities

Belongs to the MHC class I family.

Tissue Specificity

Ubiquitous.

Cellular localization

Alternative names

HLAA, HLA-A, Human leukocyte antigen A

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