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 (769 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
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune response-associated antigens, human; the immune response genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
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: Complex, Major Histocompatibility; Complices, Major Histocompatibility; Histocompatibility Complex, Major; Histocompatibility Complices, Major; Major Histocompatibility Complices; Histocompatibility Complex; Complex, Histocompatibility; Complices, Histocompatibility.
Where it fits in the MeSH classification
- Broader topics
- Genes; Genetic Loci; Immunogenetic Phenomena
- Narrower topics
- Genes, MHC Class I; Genes, MHC Class II
- See also
- Genes, MHC Class I
Related concepts
- Transplantation Antigens
- Immune Response-Associated Antigens
- Human
- Immune Response Genes
Research landscape
PubMed indexes 23,925 records tagged with the MeSH heading “Major Histocompatibility Complex” (counts retrieved 2026-10-29). 1,339 of them (5.6%) were published from 2020 onward, and the busiest period so far is through 1999 with 13,975 records.
Reviews account for 4,090 records (17.1%) and meta-analyses for 32. Randomized controlled trials number 28 (0.1%) 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 | 13,975 |
| 2000-2009 | 5,351 |
| 2010-2019 | 3,260 |
| 2020 onward | 1,339 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 4,090 | 17.1% |
| Meta-analyses | 32 | 0.1% |
| Randomized controlled trials | 28 | 0.1% |
Method: PubMed query "Major Histocompatibility Complex"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in immunology
Immune responses are studied in model organisms, in cells from donors and in patients, and the same pathway can behave differently across these settings. Mouse immune systems differ from human ones in important ways, and blood measurements may not reflect what happens in tissues. Clinical conclusions about immune-mediated disease or immunotherapy come mainly from controlled trials and long-term cohorts. Check the species and tissue studied, whether markers were linked to outcomes patients notice, and the follow-up time.
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 |
|---|---|---|---|---|
| IPD-IMGT/HLA Database | 2020 | Research article Design not recorded in structured metadata | 1,248 | cc by PMID 31667505 · DOI · PMC7145640 |
| γδ T cells are effectors of immunotherapy in cancers with HLA class I defects | 2023 | Research article Design not recorded in structured metadata | 279 | cc by PMID 36631610 · DOI · PMC9876799 |
| Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA | 2018 | Research article Design not recorded in structured metadata | 256 | cc by PMID 30250229 · DOI · PMC6155241 |
| Tumor NLRP3 amplification promotes immunotherapy resistance by inhibiting STAT1 signaling and MHC class I expression | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 42593864 · DOI · PMC13668618 |
IPD-IMGT/HLA Database [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The IPD-IMGT/HLA Database, http://www.
- Closing excerpt
- In order to do this, traditional methods of accessing and presenting data will be challenged, and new methods will need to be utilized to keep pace with new discoveries.
- 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 (191 words)
The IPD-IMGT/HLA Database, http://www.ebi.ac.uk/ipd/imgt/hla/, currently contains over 25 000 allele sequence for 45 genes, which are located within the Major Histocompatibility Complex (MHC) of the human genome. This region is the most polymorphic region of the human genome, and the levels of polymorphism seen exceed most other genes. Some of the genes have several thousand variants and are now termed hyperpolymorphic, rather than just simply polymorphic. The IPD-IMGT/HLA Database has provided a stable, highly accessible, user-friendly repository for this information, providing the scientific and medical community access to the many variant sequences of this gene system, that are critical for the successful outcome of transplantation. The number of currently known variants, and dramatic increase in the number of new variants being identified has necessitated a dedicated resource with custom tools for curation and publication. The challenge for the database is to continue to provide a highly curated database of sequence variants, while supporting the increased number of submissions and complexity of sequences. In order to do this, traditional methods of accessing and presenting data will be challenged, and new methods will need to be utilized to keep pace with new discoveries.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31667505 · DOI · PMC7145640
γδ T cells are effectors of immunotherapy in cancers with HLA class I defects [2]
Abstract reading summary — source excerpts
- Opening excerpt
- DNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint blockade (ICB)1,2.
- Closing excerpt
- Taken together, these data indicate that γδ T cells contribute to the response to immune checkpoint blockade in patients with HLA-class-I-negative MMR-d colon cancers, and underline the potential of γδ T cells in cancer immunotherapy.
- 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 (226 words)
DNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint blockade (ICB)1,2. Here, in contrast to other cancer types3-5, we observed that 20 out of 21 (95%) MMR-d cancers with genomic inactivation of β2-microglobulin (encoded by B2M) retained responsiveness to ICB, suggesting the involvement of immune effector cells other than CD8+ T cells in this context. We next identified a strong association between B2M inactivation and increased infiltration by γδ T cells in MMR-d cancers. These γδ T cells mainly comprised the Vδ1 and Vδ3 subsets, and expressed high levels of PD-1, other activation markers, including cytotoxic molecules, and a broad repertoire of killer-cell immunoglobulin-like receptors. In vitro, PD-1+ γδ T cells that were isolated from MMR-d colon cancers exhibited enhanced reactivity to human leukocyte antigen (HLA)-class-I-negative MMR-d colon cancer cell lines and B2M-knockout patient-derived tumour organoids compared with antigen-presentation-proficient cells. By comparing paired tumour samples from patients with MMR-d colon cancer that were obtained before and after dual PD-1 and CTLA-4 blockade, we found that immune checkpoint blockade substantially increased the frequency of γδ T cells in B2M-deficient cancers. Taken together, these data indicate that γδ T cells contribute to the response to immune checkpoint blockade in patients with HLA-class-I-negative MMR-d colon cancers, and underline the potential of γδ T cells in cancer immunotherapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36631610 · DOI · PMC9876799
Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Understanding mechanisms of late/acquired cancer immunotherapy resistance is critical to improve outcomes; cellular immunotherapy trials offer a means to probe complex tumor-immune interfaces through defined T cell/antigen interactions.
- Closing excerpt
- Transcriptional suppression of Class I loci may underlie resistance to other immunotherapies, including checkpoint inhibitors, and have implications for the design of improved immunotherapy treatments.
- 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 (145 words)
Understanding mechanisms of late/acquired cancer immunotherapy resistance is critical to improve outcomes; cellular immunotherapy trials offer a means to probe complex tumor-immune interfaces through defined T cell/antigen interactions. We treated two patients with metastatic Merkel cell carcinoma with autologous Merkel cell polyomavirus specific CD8+ T cells and immune-checkpoint inhibitors. In both cases, dramatic remissions were associated with dense infiltration of activated CD8+s into the regressing tumors. However, late relapses developed at 22 and 18 months, respectively. Here we report single cell RNA sequencing identified dynamic transcriptional suppression of the specific HLA genes presenting the targeted viral epitope in the resistant tumor as a consequence of intense CD8-mediated immunologic pressure; this is distinguished from genetic HLA-loss by its reversibility with drugs. Transcriptional suppression of Class I loci may underlie resistance to other immunotherapies, including checkpoint inhibitors, and have implications for the design of improved immunotherapy treatments.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30250229 · DOI · PMC6155241
Tumor NLRP3 amplification promotes immunotherapy resistance by inhibiting STAT1 signaling and MHC class I expression [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Immunotherapy resistance remains a challenge in immuno-oncology, and predictive biomarkers are needed to guide combination immunotherapy selection for the individual patient.
- Closing excerpt
- This work reveals a fundamental link between cellular stress and tumor-mediated immune evasion and indicates that the tumor NLRP3 signaling pathway merits further clinical study as a therapeutic target and a source of companion biomarkers for overcoming checkpoint inhibitor resistance in patients with cancer.
- 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 (207 words)
Immunotherapy resistance remains a challenge in immuno-oncology, and predictive biomarkers are needed to guide combination immunotherapy selection for the individual patient. We showed that elevated tumor-intrinsic NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) signaling activity correlates with checkpoint inhibitor resistance in several independent cohorts of stage III/IV melanoma and gastroesophageal (GE) adenocarcinoma. In situ hybridization demonstrated tumor NLRP3 copy number gain in immunotherapy-resistant melanomas and GE adenocarcinomas harboring enhanced NLRP3 signaling activity. Nlrp3 amplification suppressed NOD-, LRR-, and CARD-containing 5-mediated (NLRC5-mediated) MHC class I upregulation, while spatial transcriptomic analysis of patient-derived GE adenocarcinomas confirmed that NLRP3 signaling activity inversely correlated with NLRC5 and MHC class I-associated gene expression. Mechanistically, NLRP3 binds to and inhibits signal transducer and activator of transcription 1 (STAT1) dimerization, nuclear translocation, and NLRC5 transcription. Consistent with these findings, pharmacologic inhibition of the NLRP3 inflammasome augmented tumor STAT1/NLRC5 signaling, enhanced MHC class I surface expression, and overcame anti-programmed cell death 1 resistance in an orthotopic model of gastric adenocarcinoma. This work reveals a fundamental link between cellular stress and tumor-mediated immune evasion and indicates that the tumor NLRP3 signaling pathway merits further clinical study as a therapeutic target and a source of companion biomarkers for overcoming checkpoint inhibitor resistance in patients with cancer.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42593864 · DOI · PMC13668618
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 Major histocompatibility complex genomics and human disease [5]
- Research article Antigen-presentation properties of plasmacytoid dendritic cells [6]
- Research article NLRC5: a key regulator of MHC class I-dependent immune responses [7]
- Research article Insights into the initiation of TCR signaling [8]
- Research article Mechanisms maintaining peripheral tolerance [9]
- Research article Advances in the Evolutionary Understanding of MHC Polymorphism [10]
References
- Robinson J, Barker DJ, Georgiou X, Cooper MA, Flicek P, Marsh SGE. IPD-IMGT/HLA Database. . 2020. PMID 31667505 · DOI · PMC7145640
- de Vries NL, van de Haar J, Veninga V, Chalabi M, Ijsselsteijn ME, van der Ploeg M, et al.. γδ T cells are effectors of immunotherapy in cancers with HLA class I defects. . 2023. PMID 36631610 · DOI · PMC9876799
- Paulson KG, Voillet V, McAfee MS, Hunter DS, Wagener FD, Perdicchio M, et al.. Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA. . 2018. PMID 30250229 · DOI · PMC6155241
- Theivanthiran B, Yarla N, Villarreal K, Nguyen YV, Rezazade Bazaz M, Pena Calderin E, et al.. Tumor NLRP3 amplification promotes immunotherapy resistance by inhibiting STAT1 signaling and MHC class I expression. . 2026. PMID 42593864 · DOI · PMC13668618
- Trowsdale J, Knight JC. Major histocompatibility complex genomics and human disease. Annu Rev Genomics Hum Genet. 2013. PMID 23875801 · DOI · PMC4426292
- Villadangos JA, Young L. Antigen-presentation properties of plasmacytoid dendritic cells. Immunity. 2008. PMID 18799143 · DOI
- Kobayashi KS, van den Elsen PJ. NLRC5: a key regulator of MHC class I-dependent immune responses. Nat Rev Immunol. 2012. PMID 23175229 · DOI
- Chakraborty AK, Weiss A. Insights into the initiation of TCR signaling. Nat Immunol. 2014. PMID 25137454 · DOI · PMC5226627
- Mueller DL. Mechanisms maintaining peripheral tolerance. Nat Immunol. 2010. PMID 20016506 · DOI
- Radwan J, Babik W, Kaufman J, Lenz TL, Winternitz J. Advances in the Evolutionary Understanding of MHC Polymorphism. Trends Genet. 2020. PMID 32044115 · DOI
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 2026-10-29.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
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.