ArticlePLoS computational biology2012
Degenerate T-cell recognition of peptides on MHC molecules creates large holes in the T-cell repertoire.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up.Journal for immunotherapy of cancer · 2020Trial
- Machine learning-based prediction of cross-immunity.Briefings in bioinformatics · 2026Article
- Central T cell tolerance from sparse peptide sampling.Science advances · 2026Article
- Deep Mutational Scanning in Immunology: Techniques and Applications.Pathogens (Basel, Switzerland) · 2025Review
- Properties of CD8 T-cell-recognized neoantigens in different tumor types.Immuno-oncology technology · 2025Article
- NetMHCpan-4.2: improved prediction of CD8+ epitopes by use of transfer learning and structural features.Frontiers in immunology · 2025Article
- Predicting T cell receptor functionality against mutant epitopes.Cell genomics · 2024Article
- A journey to your self: The vague definition of immune self and its practical implications.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens.Frontiers in immunology · 2024Article
- A transfer-learning approach to predict antigen immunogenicity and T-cell receptor specificity.eLife · 2023Article
- Article
- Determinants of tumor immune evasion: the role of T cell exposed motif frequency and mutant amino acid exposure.Frontiers in immunology · 2023Article
- A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Degeneracy measures in biologically plausible random Boolean networks.BMC bioinformatics · 2022Article
- Mechanistic diversity in MHC class I antigen recognition.The Biochemical journal · 2021Review
- Article
- Unique Pathogen Peptidomes Facilitate Pathogen-Specific Selection and Specialization of MHC Alleles.Molecular biology and evolution · 2021Article
- Self-mediated positive selection of T cells sets an obstacle to the recognition of nonself.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Strength and Numbers: The Role of Affinity and Avidity in the 'Quality' of T Cell Tolerance.Cells · 2021Review
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cellular immune system screens peptides presented by host cells on MHC molecules to assess if the cells are infected. In this study we examined whether the presented peptides contain enough information for a proper self/nonself assessment by comparing the presented human (self) and bacterial or viral (nonself) peptides on a large number of MHC molecules. For all MHC molecules tested, only a small fraction of the presented nonself peptides from 174 species of bacteria and 1000 viral proteomes ([Formula: see text]0.2%) is shown to be identical to a presented self peptide. Next, we use available data on T-cell receptor-peptide-MHC interactions to estimate how well T-cells distinguish between similar peptides. The recognition of a peptide-MHC by the T-cell receptor is flexible, and as a result, about one-third of the presented nonself peptides is expected to be indistinguishable (by T-cells) from presented self peptides. This suggests that T-cells are expected to remain tolerant for a large fraction of the presented nonself peptides, which provides an explanation for the "holes in the T-cell repertoire" that are found for a large fraction of foreign epitopes. Additionally, this overlap with self increases the need for efficient self tolerance, as many self-similar nonself peptides could initiate an autoimmune response. Degenerate recognition of peptide-MHC-I complexes by T-cells thus creates large and potentially dangerous overlaps between self and nonself.
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