ArticleProceedings of the National Academy of Sciences of the United States of America2009
Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Minor histocompatibility antigen TCR-T.Blood advances · 2026Review
- High-throughput cloning reveals diverse properties of T-cell receptors targeting minor histocompatibility antigens.Blood advances · 2026Article
- Dynamical network analysis reveals long-range residue couplings at the pMHC interface underlying enhanced immunogenicity.NPJ systems biology and applications · 2026Article
- Immunoinformatics-Based Design of Multi-epitope DNA and mRNA Vaccines Against Zika Virus.Bioinformatics and biology insights · 2024Article
- Charge-based interactions through peptide position 4 drive diversity of antigen presentation by human leukocyte antigen class I molecules.PNAS nexus · 2022Article
- Structural Prediction of Peptide-MHC Binding Modes.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Targeting Neoepitopes to Treat Solid Malignancies: Immunosurgery.Frontiers in immunology · 2021Review
- TCR Recognition of Peptide-MHC-I: Rule Makers and Breakers.International journal of molecular sciences · 2020Review
- Peptide mimotopes alter T cell function in cancer and autoimmunity.Seminars in immunology · 2020Review
- Minor Histocompatibility Antigen-Specific T Cells.Frontiers in pediatrics · 2020Review
- The potential HLA Class I-restricted epitopes derived from LeIF and TSA of Leishmania donovani evoke anti-leishmania CD8+ T lymphocyte response.Scientific reports · 2018Article
- Article
- Pan-Specific Prediction of Peptide-MHC Class I Complex Stability, a Correlate of T Cell Immunogenicity.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Article
- Proteome changes in the small intestinal mucosa of broilers (Gallus gallus) induced by high concentrations of atmospheric ammonia.Proteome science · 2015Article
- Transplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance.Nature communications · 2014Article
- Minor histocompatibility antigens and the maternal immune response to the fetus during pregnancy.American journal of reproductive immunology (New York, N.Y. : 1989) · 2013Review
- Effect of MHC and non-MHC donor/recipient genetic disparity on the outcome of allogeneic HCT.Blood · 2012Review
- Augmentation of anti-tumor immunity by adoptive T-cell transfer after allogeneic hematopoietic stem cell transplantation.Expert review of hematology · 2012Review
- Structural and energetic evidence for highly peptide-specific tumor antigen targeting via allo-MHC restriction.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
T cell recognition of minor histocompatibility antigens (mHags) underlies allogeneic immune responses that mediate graft-versus-host disease and the graft-versus-leukemia effect following stem cell transplantation. Many mHags derive from single amino acid polymorphisms in MHC-restricted epitopes, but our understanding of the molecular mechanisms governing mHag immunogenicity and recognition is incomplete. Here we examined antigenic presentation and T-cell recognition of HA-1, a prototypic autosomal mHag derived from single nucleotide dimorphism (HA-1(H) versus HA-1(R)) in the HMHA1 gene. The HA-1(H) peptide is restricted by HLA-A2 and is immunogenic in HA-1(R/R) into HA-1(H) transplants, while HA-1(R) has been suggested to be a "null allele" in terms of T cell reactivity. We found that proteasomal cleavage and TAP transport of the 2 peptides is similar and that both variants can bind to MHC. However, the His>Arg change substantially decreases the stability and affinity of HLA-A2 association, consistent with the reduced immunogenicity of the HA-1(R) variant. To understand these findings, we determined the structure of an HLA-A2-HA-1(H) complex to 1.3A resolution. Whereas His-3 is accommodated comfortably in the D pocket, incorporation of the lengthy Arg-3 is predicted to require local conformational changes. Moreover, a soluble TCR generated from HA-1(H)-specific T-cells bound HA-1(H) peptide with moderate affinity but failed to bind HA-1(R), indicating complete discrimination of HA-1 variants at the level of TCR/MHC interaction. Our results define the molecular mechanisms governing immunogenicity of HA-1, and highlight how single amino acid polymorphisms in mHags can critically affect both MHC association and TCR recognition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.