1. Direct recognition of an intact foreign protein by an αβ T cell receptor.
- Author
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Almeida, Catarina F., Gully, Benjamin S., Jones, Claerwen M., Kedzierski, Lukasz, Gunasinghe, Sachith D., Rice, Michael T., Berry, Richard, Gherardin, Nicholas A., Nguyen, Trang T., Mok, Yee-Foong, Reijneveld, Josephine F., Moody, D. Branch, Van Rhijn, Ildiko, La Gruta, Nicole L., Uldrich, Adam P., Rossjohn, Jamie, and Godfrey, Dale I.
- Subjects
MAJOR histocompatibility complex ,T cells ,MOLECULAR interactions ,CRYSTAL structure ,T cell receptors ,GLOBIN ,THYMUS - 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. Certain specific antigens have been shown to activate T cells in an MHC independent manner. Here the authors show a phycoerythrin reactive mouse TCR which recognises native protein and characterise the molecular nature of this interaction and that this specific TCR can be selected in the thymus. [ABSTRACT FROM AUTHOR]- Published
- 2024
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