Journal article

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

CF Almeida, BS Gully, CM Jones, L Kedzierski, SD Gunasinghe, MT Rice, R Berry, NA Gherardin, TT Nguyen, YF Mok, JF Reijneveld, DB Moody, I Van Rhijn, NL La Gruta, AP Uldrich, J Rossjohn, DI Godfrey

Nature Communications | Published : 2024

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 comple..

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