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)6γ 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.
Original language | English |
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Article number | 8816 |
Number of pages | 18 |
Journal | Nature Communications |
Volume | 15 |
Issue number | 1 |
DOIs | |
Publication status | Published - Dec 2024 |
Equipment
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Animal Research Platform (MARP)
Christine Findlay (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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Australian Synchrotron
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility
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Macromolecular Crystallisation Facility
Geoffrey Kong (Operator)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility