Projects per year
Abstract
Central to adaptive immunity is the interaction between the alphabeta T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iTreg) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 180 degrees polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iTreg TCR alpha-chain and beta-chain are overlaid with the alpha-chain and beta-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not hardwired to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition.
Original language | English |
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Pages (from-to) | 1153 - 1161 |
Number of pages | 9 |
Journal | Nature Immunology |
Volume | 16 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2015 |
Projects
- 3 Finished
-
ARC Centre of Excellence in Advanced Molecular Imaging
Whisstock, J., Abbey, B., Nugent, K., Quiney, H. M., Godfrey, D. I., Heath, W., Fairlie, D., Chapman, H., Peele, A., Davey, J. & Wittmann, A.
30/06/14 → 31/03/21
Project: Research
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Antigen presentation during HLA B27 associated autoimmune disease
National Health and Medical Research Council (NHMRC) (Australia)
1/01/12 → 31/12/14
Project: Research