Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (810 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: HLA A Antigens; HLA-A; Antigens, HLA-A; Antigens, HLA A.
Where it fits in the MeSH classification
- Broader topics
- Histocompatibility Antigens Class I; HLA Antigens
- Narrower topics
- HLA-A1 Antigen; HLA-A11 Antigen; HLA-A2 Antigen; HLA-A24 Antigen; HLA-A3 Antigen
Research landscape
PubMed indexes 10,171 records tagged with the MeSH heading “HLA-A Antigens” (counts retrieved 2026-10-31). 1,372 of them (13.5%) were published from 2020 onward, and the busiest period so far is 2000-2009 with 3,216 records.
Reviews account for 277 records (2.7%) and meta-analyses for 30. Randomized controlled trials number 56 (0.6%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 3,156 |
| 2000-2009 | 3,216 |
| 2010-2019 | 2,427 |
| 2020 onward | 1,372 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 277 | 2.7% |
| Meta-analyses | 30 | 0.3% |
| Randomized controlled trials | 56 | 0.6% |
Method: PubMed query "HLA-A Antigens"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Suboptimal SARS-CoV-2-specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype | 2020 | Research article Design not recorded in structured metadata | 176 | cc by PMID 32913053 · DOI · PMC7533701 |
| SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses | 2021 | Research article Design not recorded in structured metadata | 156 | cc by PMID 33664060 · DOI · PMC8224398 |
| Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19 | 2021 | Research article Design not recorded in structured metadata | 106 | cc by PMID 33732261 · DOI · PMC7959787 |
| Dual CD8 and TCR editing in regulatory T cells mediates HLA-A2-restricted tissue-specific homing | 2026 | Research article Design not recorded in structured metadata | 3 | cc by PMID 41709576 · DOI · PMC13239781 |
Suboptimal SARS-CoV-2-specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype [1]
Abstract reading summary — source excerpts
- Opening excerpt
- An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies.
- Closing excerpt
- Priming with appropriate vaccines may thus be beneficial for optimizing CD8+ T cell immunity in COVID-19.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (246 words)
An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8+ T cell memory to peptides presented by common HLA types like HLA-A2, which enhances recovery and diminishes clinical severity upon reinfection. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the clonal expansion of SARS-CoV-2-specific CD8+ and CD4+ T cells in vitro, with CD4+ T cells being robust. We identified two HLA-A*02:01-restricted SARS-CoV-2-specfic CD8+ T cell epitopes, A2/S269-277 and A2/Orf1ab3183-3191 Using peptide-HLA tetramer enrichment, direct ex vivo assessment of A2/S269+CD8+ and A2/Orf1ab3183+CD8+ populations indicated that A2/S269+CD8+ T cells were detected at comparable frequencies (∼1.3 × 10-5) in acute and convalescent HLA-A*02:01+ patients. These frequencies were higher than those found in uninfected HLA-A*02:01+ donors (∼2.5 × 10-6), but low when compared to frequencies for influenza-specific (A2/M158) and Epstein-Barr virus (EBV)-specific (A2/BMLF1280) (∼1.38 × 10-4) populations. Phenotyping A2/S269+CD8+ T cells from COVID-19 convalescents ex vivo showed that A2/S269+CD8+ T cells were predominantly negative for CD38, HLA-DR, PD-1, and CD71 activation markers, although the majority of total CD8+ T cells expressed granzymes and/or perforin. Furthermore, the bias toward naïve, stem cell memory and central memory A2/S269+CD8+ T cells rather than effector memory populations suggests that SARS-CoV-2 infection may be compromising CD8+ T cell activation. Priming with appropriate vaccines may thus be beneficial for optimizing CD8+ T cell immunity in COVID-19.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32913053 · DOI · PMC7533701
SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses [2]
Abstract reading summary — source excerpts
- Opening excerpt
- CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control.
- Closing excerpt
- Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through point mutations in MHC-I-restricted viral epitopes.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (119 words)
CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified nonsynonymous mutations in MHC-I-restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding in a cell-free in vitro assay. Reduced MHC-I binding of mutant peptides was associated with decreased proliferation, IFN-γ production and cytotoxic activity of CD8+ T cells isolated from HLA-matched COVID-19 patients. Single cell RNA sequencing of ex vivo expanded, tetramer-sorted CD8+ T cells from COVID-19 patients further revealed qualitative differences in the transcriptional response to mutant peptides. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through point mutations in MHC-I-restricted viral epitopes.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33664060 · DOI · PMC8224398
Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19 [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Human leukocyte antigen (HLA) class I molecules play a crucial role in the development of a specific immune response to viral infections by presenting viral peptides at the cell surface where they will be further recognized by T cells.
- Closing excerpt
- The obtained results suggest the important role of HLA class I peptide presentation in the development of a specific immune response to COVID-19.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (298 words)
Human leukocyte antigen (HLA) class I molecules play a crucial role in the development of a specific immune response to viral infections by presenting viral peptides at the cell surface where they will be further recognized by T cells. In the present manuscript, we explored whether HLA class I genotypes can be associated with the critical course of Coronavirus Disease-19 by searching possible connections between genotypes of deceased patients and their age at death. HLA-A, HLA-B, and HLA-C genotypes of n = 111 deceased patients with COVID-19 (Moscow, Russia) and n = 428 volunteers were identified with next-generation sequencing. Deceased patients were split into two groups according to age at the time of death: n = 26 adult patients aged below 60 and n = 85 elderly patients over 60. With the use of HLA class I genotypes, we developed a risk score (RS) which was associated with the ability to present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides by the HLA class I molecule set of an individual. The resulting RS was significantly higher in the group of deceased adults compared to elderly adults [p = 0.00348, area under the receiver operating characteristic curve (AUC ROC = 0.68)]. In particular, presence of HLA-A*01:01 allele was associated with high risk, while HLA-A*02:01 and HLA-A*03:01 mainly contributed to low risk. The analysis of patients with homozygosity strongly highlighted these results: homozygosity by HLA-A*01:01 accompanied early deaths, while only one HLA-A*02:01 homozygote died before 60 years of age. Application of the constructed RS model to an independent Spanish patients cohort (n = 45) revealed that the score was also associated with the severity of the disease. The obtained results suggest the important role of HLA class I peptide presentation in the development of a specific immune response to COVID-19.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33732261 · DOI · PMC7959787
Dual CD8 and TCR editing in regulatory T cells mediates HLA-A2-restricted tissue-specific homing [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Type 1 diabetes (T1D) is marked by the overexpression of class I major histocompatibility complex (MHC) antigens in pancreatic islets, which are targeted by islet-specific CD8+ T cells.
- Closing excerpt
- This approach demonstrates that TCR specificity, reflected by its functional activity, is crucial for tissue-specific trafficking, paving the way to improve the efficacy of Treg therapies for T1D.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (147 words)
Type 1 diabetes (T1D) is marked by the overexpression of class I major histocompatibility complex (MHC) antigens in pancreatic islets, which are targeted by islet-specific CD8+ T cells. Here, we aimed to improve regulatory T cell (Treg) infiltration into pancreatic islets by redirecting their specificity toward class I-restricted islet antigens. We functionally validated two islet-specific HLA-A2 (∗02:01)-restricted T cell receptors (TCRs), one specific for ZnT8186-194 (clone D222D) and the second for IGRP265-273 (clone 32), by dual-locus (TRAC/CD4) homology-directed editing. Clone D222D was peptide specific and CD8αβ dependent, while clone 32 exhibited antigen promiscuity and showed CD8α dependency. Engineered CD4to8 TCR Tregs maintained stable phenotypes, in vitro suppressive function compared to their polyclonal counterparts, and showed co-receptor-dependent migration in vivo. This approach demonstrates that TCR specificity, reflected by its functional activity, is crucial for tissue-specific trafficking, paving the way to improve the efficacy of Treg therapies for T1D.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41709576 · DOI · PMC13239781
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism [5]
- Research article The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases [6]
- Research article HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis [7]
- Research article Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions [8]
- Research article HLA-B27 and HLA-A2 subtypes: structure, evolution and function [9]
- Research article HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions [10]
References
- Habel JR, Nguyen THO, van de Sandt CE, Juno JA, Chaurasia P, Wragg K, et al.. Suboptimal SARS-CoV-2-specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype. . 2020. PMID 32913053 · DOI · PMC7533701
- Agerer B, Koblischke M, Gudipati V, Montaño-Gutierrez LF, Smyth M, Popa A, et al.. SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses. . 2021. PMID 33664060 · DOI · PMC8224398
- Shkurnikov M, Nersisyan S, Jankevic T, Galatenko A, Gordeev I, Vechorko V, et al.. Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19. . 2021. PMID 33732261 · DOI · PMC7959787
- Porret R, Lebreton F, Pace E, Stefanidis E, Semilietof A, Guillaume P, et al.. Dual CD8 and TCR editing in regulatory T cells mediates HLA-A2-restricted tissue-specific homing. . 2026. PMID 41709576 · DOI · PMC13239781
- Sette A, Sidney J. Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism. Immunogenetics. 1999. PMID 10602880 · DOI
- Price P, Witt C, Allcock R, Sayer D, Garlepp M, Kok CC, et al.. The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases. Immunol Rev. 1999. PMID 10319267 · DOI
- Genin E, Chen DP, Hung SI, Sekula P, Schumacher M, Chang PY, et al.. HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis. Pharmacogenomics J. 2014. PMID 24322785 · DOI
- Amstutz U, Shear NH, Rieder MJ, Hwang S, Fung V, Nakamura H, et al.. Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions. Epilepsia. 2014. PMID 24597466 · DOI
- López de Castro JA. HLA-B27 and HLA-A2 subtypes: structure, evolution and function. Immunol Today. 1989. PMID 2679637 · DOI
- Shi YW, Min FL, Zhou D, Qin B, Wang J, Hu FY, et al.. HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions. Neurology. 2017. PMID 28476759 · DOI · PMC5467955
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.