ArticleProceedings of the National Academy of Sciences of the United States of America2021
Self-mediated positive selection of T cells sets an obstacle to the recognition of nonself.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- C > U mutations generate immunogenic peptides in SARS-CoV-2.Nature communications · 2025Article
- Computational identification of cross-reactive TCR epitopes with ARDitox.Journal of cancer research and clinical oncology · 2025Article
- Similarity to Self-Antigens Shapes Epitope Recognition from Viruses Under Autoimmune and Infectious Disease.International journal of molecular sciences · 2025Article
- 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
- Tetanus-diphtheria vaccine can prime SARS-CoV-2 cross-reactive T cells.Frontiers in immunology · 2024Article
- A robust deep learning workflow to predict CD8 + T-cell epitopes.Genome medicine · 2023Article
- A Framework for Understanding Maternal Immunity.Immunology and allergy clinics of North America · 2023Review
- Determinants of tumor immune evasion: the role of T cell exposed motif frequency and mutant amino acid exposure.Frontiers in immunology · 2023Article
- Evaluating performance of existing computational models in predicting CD8+ T cell pathogenic epitopes and cancer neoantigens.Briefings in bioinformatics · 2022Article
- Review
- High Throughput Human T Cell Receptor Sequencing: A New Window Into Repertoire Establishment and Alloreactivity.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adaptive immune recognition is mediated by the binding of peptide-human leukocyte antigen complexes by T cells. Positive selection of T cells in the thymus is a fundamental step in the generation of a responding T cell repertoire: only those T cells survive that recognize human peptides presented on the surface of cortical thymic epithelial cells. We propose that while this step is essential for optimal immune function, the process results in a defective T cell repertoire because it is mediated by self-peptides. To test our hypothesis, we focused on amino acid motifs of peptides in contact with T cell receptors. We found that motifs rarely or not found in the human proteome are unlikely to be recognized by the immune system just like the ones that are not expressed in cortical thymic epithelial cells or not presented on their surface. Peptides carrying such motifs were especially dissimilar to human proteins. Importantly, we present our main findings on two independent T cell activation datasets and directly demonstrate the absence of naïve T cells in the repertoire of healthy individuals. We also show that T cell cross-reactivity is unable to compensate for the absence of positively selected T cells. Additionally, we show that the proposed mechanism could influence the risk for different infectious diseases. In sum, our results suggest a side effect of T cell positive selection, which could explain the nonresponsiveness to many nonself peptides and could improve the understanding of adaptive immune recognition.
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