Direct recognition of an intact foreign protein by an αβ T cell receptor.

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    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
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      Original Publication: [London] : Nature Pub. Group
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    • Abstract:
      αβ T cell receptors (αβTCRs) co-recognise antigens when bound to Major Histocompatibility Complex (MHC) or MHC class I-like molecules. Additionally, some αβTCRs can bind non-MHC molecules, but how much intact antigen reactivities are achieved remains unknown. Here, we identify an αβ T cell clone that directly recognises the intact foreign protein, R-phycoerythrin (PE), a multimeric (αβ) 6 γ protein complex. This direct αβTCR-PE interaction occurs in an MHC-independent manner, yet triggers T cell activation and bound PE with an affinity comparable to αβTCR-peptide-MHC interactions. The crystal structure reveals how six αβTCR molecules simultaneously engage the PE hexamer, mediated by the complementarity-determining regions (CDRs) of the αβTCR. Here, the αβTCR mainly binds to two α-helices of the globin fold in the PE α-subunit, which is analogous to the antigen-binding platform of the MHC molecule. Using retrogenic mice expressing this TCR, we show that it supports intrathymic T cell development, maturation, and exit into the periphery as mature CD4/CD8 double negative (DN) T cells with TCR-mediated functional capacity. Accordingly, we show how an αβTCR can recognise an intact foreign protein in an antibody-like manner.
      (© 2024. The Author(s).)
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    • Accession Number:
      0 (Receptors, Antigen, T-Cell, alpha-beta)
      11016-17-4 (Phycoerythrin)
      0 (Complementarity Determining Regions)
    • Publication Date:
      Date Created: 20241011 Date Completed: 20241011 Latest Revision: 20241014
    • Publication Date:
      20241015
    • Accession Number:
      PMC11470135
    • Accession Number:
      10.1038/s41467-024-51897-3
    • Accession Number:
      39394178