更新于：2024-05-01
HLA-A
major histocompatibility complex, class I, A
更新于：2024-05-01
基本信息
别名 HLA class I histocompatibility antigen, A alpha chain、HLA-A、HLAA + [2] |
简介 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:2456340, PubMed:2784196, PubMed:1402688, PubMed:7504010, PubMed:9862734, PubMed:10449296, PubMed:12138174, PubMed:12393434, PubMed:15893615, PubMed:17189421, PubMed:19543285, PubMed:21498667, PubMed:24192765, PubMed:7694806, PubMed:24395804, PubMed:28250417). 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:17189421, PubMed:20364150, PubMed:17079320, 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*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*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*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:9047241, PubMed:12393434, PubMed:24192765, PubMed:20844028). 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*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:7504010, PubMed:17189421, PubMed:20364150, PubMed:25880248, PubMed:30530481, PubMed:19177349, PubMed:24395804, PubMed:26758806, PubMed:32887977). 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*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*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*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*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*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:7504010, PubMed:7679507, PubMed:9862734, PubMed:19543285, PubMed:21943705, PubMed:2456340, PubMed:32887977). 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*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.
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. |
关联
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
100 项与 HLA-A 相关的临床结果
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100 项与 HLA-A 相关的转化医学
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2024-02-24Annals of neurology
Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Is Associated with HLA-A*3303 and HLA-DPB1*0501.
Article
作者: Yaqing Shu ; Renliang Huang ; Qihui Li ; Yi Lu ; Junping Yin ; Huilu Li ; Zhike Lan ; Xiujun Zheng ; Jinlong Ye ; Youming Long ; Zhanhang Wang ; Li Xiao ; Qiaomiao Zhou ; Xu Liu ; Ying Fu ; Hao Chen ; Juanjuan Chen ; Yanxia Zhou ; Juan Zhou ; Liting Zhang ; Jing Zhou ; Ying Jiang ; Fuhua Peng ; Zhengqi Lu ; Frank Petersen ; Wei Qiu ; Xinhua Yu
We determined the genetic association between specific human leucocyte antigen (HLA) loci and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Our results showed that autoimmune GFAP astrocytopathy was associated with HLA-A*3303 (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.32-3.06, p = 0.00072, padj. = 0.046) and HLA-DBP1*0501 (OR = 0.51, 95% CI = 0.36-0.71, p = 0.000048, padj. = 0.0062). Moreover, HLA-A*3303 carriers with the disease had a longer hospital stay (p = 0.0005) than non-carriers. This study for the first time provides evidence for a role of genetic factor in the development of autoimmune GFAP astrocytopathy. ANN NEUROL 2024.
2024-02-22Neuroscience
Bioinformatics and Systems Biology Approaches to Identify the Synergistic Effects of Alcohol Use Disorder on the Progression of Neurological Diseases.
Article
作者: Md Jahangir Alam ; Md Habibur Rahman ; Md Arju Hossain ; Md Robiul Hoque ; Md Aktaruzzaman
Clinical investigations showed that individuals with Alcohol Use Disorder (AUD) have worse Neurological Disease (ND) development, pointing to possible pathogenic relationships between AUD and NDs. It remains difficult to identify risk factors that are predisposing between AUD and NDs. In order to fix these issues, we created the bioinformatics pipeline and network-based approaches for employing unbiased methods to discover genes abnormally stated in both AUD and NDs and to pinpoint some of the common molecular pathways that might underlie AUD and ND interaction. We found 100 differentially expressed genes (DEGs) in both the AUD and ND patient's tissue samples. The most important Gene Ontology (GO) terms and metabolic pathways, including positive control of cytotoxicity caused by T cells, proinflammatory responses, antigen processing and presentation, and platelet-triggered interactions with vascular and circulating cell pathways were then extracted using the overlapped DEGs. Protein-protein interaction analysis was used to identify hub proteins, including CCL2, IL1B, TH, MYCN, HLA-DRB1, SLC17A7, and HNF4A, in the pathways that have been reported as playing a function in these disorders. We determined several TFs (HNF4A, C4A, HLA-B, SNCA, HLA-DMB, SLC17A7, HLA-DRB1, HLA-C, HLA-A, and HLA-DPB1) and potential miRNAs (hsa-mir-34a-5p, hsa-mir-34c-5p, hsa-mir-449a, hsa-mir-155-5p, and hsa-mir-1-3p) were crucial for regulating the expression of AUD and ND which could serve as prospective targets for treatment. Our methodologies discovered unique putative biomarkers that point to the interaction between AUD and various neurological disorders, as well as pathways that could one day be the focus of therapeutic intervention.
2024-02-21British journal of haematology
HLA peptide-binding pocket diversity modulates immunological complications after cord blood transplant in acute leukaemia.
Article
作者: Wahid Boukouaci ; Monica M Rivera-Franco ; Fernanda Volt ; Mohamed Lajnef ; Ching-Lien Wu ; Hanadi Rafii ; Barbara Cappelli ; Graziana Maria Scigliuolo ; Chantal Kenzey ; Annalisa Ruggeri ; Vanderson Rocha ; Eliane Gluckman ; Ryad Tamouza
Pocket motifs and their amino acid positions of HLA molecules are known to govern antigen presentation to effector cells. Our objective was to analyse their influence on the risk of graft-versus-host disease (GVHD) and relapse after umbilical cord blood transplant (UCBT). The transplant characteristics of 849 patients with acute leukaemia were obtained from the Eurocord/EBMT database. Higher acute (a) GVHD was associated with homozygosity of UCB HLA-C amino acid positions 77 and 80 (NN/KK) (p = 0.008). Severe aGVHD was associated with HLA-A pocket B YSAVMENVHY motif (p = 0.002) and NN and RR genotypes of the HLA-C amino acid positions 77 and 156 (p = 0.006 and p = 0.002). Such risk was also increased in case of recipient and UCB mismatches in P4 (p < 0.0001) and P9 (p = 0.003) pockets of HLA-DQB1 alleles. For chronic GVHD, the pocket B YYAVMEISNY motif of the HLA-B*15:01 allele and the absence of mismatch between recipient and UCB in the P6 pocket of HLA-DRB1 were associated with a lower risk (p = 0.0007 and p = 0.0004). In relapse, both UCB pocket B YFAVMENVHY belonging to HLA-A*32:01 and recipient pocket B YDSVGENYQY motif of the HLA-C*07:01 allele were associated with higher risk (p = 0.0026 and p = 0.015). We provide clues on HLA-mediated cellular interactions and their role in the development of GVHD and relapse.
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