Covalent TCR-peptide-MHC interactions induce T cell activation and redirect T cell fate in the thymus

C Szeto; P Zareie; RC Wirasinha; JB Zhang; AT Nguyen; A Riboldi-Tunnicliffe; NL La Gruta; S Gras; SR Daley

Journal article

Covalent TCR-peptide-MHC interactions induce T cell activation and redirect T cell fate in the thymus

C Szeto, P Zareie, RC Wirasinha, JB Zhang, AT Nguyen, A Riboldi-Tunnicliffe, NL La Gruta, S Gras, SR Daley

Nature Communications | Published : 2022

DOI: 10.1038/s41467-022-32692-4

Abstract

Interactions between a T cell receptor (TCR) and a peptide-major histocompatibility complex (pMHC) ligand are typically mediated by noncovalent bonds. By studying T cells expressing natural or engineered TCRs, here we describe covalent TCR-pMHC interactions that involve a cysteine-cysteine disulfide bond between the TCR and the peptide. By introducing cysteines into a known TCR-pMHC combination, we demonstrate that disulfide bond formation does not require structural rearrangement of the TCR or the peptide. We further show these disulfide bonds still form even when the initial affinity of the TCR-pMHC interaction is low. Accordingly, TCR-peptide disulfide bonds facilitate T cell activation b..

View full abstract

University of Melbourne Researchers

Pirooz Zareie Author

Related Projects (1)

LIMITING THE IMPACT OF INFLUENZA

The development of better ways to prevent and treat influenza infection will be a major step forward in lessening the impact of the virus in..

Grants

Awarded by National Jewish Health

Funding Acknowledgements

We thank the Monash University platforms for Animal Research, Histology, FlowCore, Macro Molecular Crystallisation facility, and Micromon for their services. We thank Dr Philippa Marrack (National Jewish Health, Denver, CO) for the 5KC cell line; Dr Ken Rock (University of Massachusetts, Worchester, MA) for the DC2.4 cell line; Dr Nicholas Gascoigne (National University of Singapore, Singapore) for the mouse CD8 alpha beta constructs; Dr Dario Vignali (University of Pittsburgh, Pittsburgh, PA) for the pMIG II, pMIG II-mouseCD3, pEQ-Pam3(-E), and pVSVG vectors; and the MX team for assistance at the Australian Synchrotron. This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of ANSTO, and made use of the ACRF detector. This research was funded by Monash Biomedicine Discovery Institute (SRD), National Health and Medical Research Council [grants 1107464 and 1188589 (SRD), grant 1159272 (SG) and grants 1071916 and 1182086 (NLLG)], and Australian Research Council [grants DP170103631, DP200102776 and FT170100174 (NLLG)].