ArticleProceedings of the National Academy of Sciences of the United States of America2019
Inherent reactivity of unselected TCR repertoires to peptide-MHC molecules.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- HLA alleles shape distinct biases in the usage preferences of TCR VFrontiers in immunology · 2026Article
- The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.Immunological reviews · 2025Review
- Tracking the role of Aire in immune tolerance to the eye with a TCR transgenic mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- T-cell virtuosity in ''knowing thyself".Frontiers in immunology · 2024Review
- Article
- Evolutionary trade-offs constraining the MHC gene expansion: beyond simple TCR depletion model.Frontiers in immunology · 2023Article
- A class-mismatched TCR bypasses MHC restriction via an unorthodox but fully functional binding geometry.Nature communications · 2022Article
- Integrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA).Nature biotechnology · 2022Article
- Tetraploid Ancestry Provided Atlantic Salmon With Two Paralogue Functional T Cell Receptor Beta Regions Whereof One Is Completely Novel.Frontiers in immunology · 2022Article
- Structure of MHC-Independent TCRs and Their Recognition of Native Antigen CD155.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- MHC Restriction: Where Are We Now?Viral immunology · 2020Article
- Genetic and environmental determinants of human TCR repertoire diversity.Immunity & ageing : I & A · 2020Article
- Selected before selection: A case for inherent antigen bias in the T cell receptor repertoire.Current opinion in systems biology · 2019Article
- T cell antigen recognition: Evolution-driven affinities.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The repertoire of αβ T cell antigen receptors (TCRs) on mature T cells is selected in the thymus where it is rendered both self-tolerant and restricted to the recognition of major histocompatibility complex molecules presenting peptide antigens (pMHC). It remains unclear whether germline TCR sequences exhibit an inherent bias to interact with pMHC prior to selection. Here, we isolated TCR libraries from unselected thymocytes and upon reexpression of these random TCR repertoires in recipient T cell hybridomas, interrogated their reactivities to antigen-presenting cell lines. While these random TCR combinations could potentially have reacted with any surface molecule on the cell lines, the hybridomas were stimulated most frequently by pMHC ligands. The nature and CDR3 loop composition of the TCRβ chain played a dominant role in determining pMHC-reactivity. Replacing the germline regions of mouse TCRβ chains with those of other jawed vertebrates preserved reactivity to mouse pMHC. Finally, introducing the CD4 coreceptor into the hybridomas increased the proportion of cells that could respond to pMHC ligands. Thus, αβ TCRs display an intrinsic and evolutionary conserved bias for pMHC molecules in the absence of any selective pressure, which is further strengthened in the presence of coreceptors.
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