Understanding the complexity and malleability of T-cell recognition

John J Miles, James McCluskey, Jamie Rossjohn, Stephanie Gras

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)


T cells are the master regulators of immune system function, continually walking the biological tightrope between adequate host defence and accidental host pathology. Tolerance is maintained or broken through an intricate structural interplay between the T-cell receptor (TCR) and major histocompatibility complex (MHC) molecule cradling peptide antigens (p). Recent advances in structural biology have shown that the TCR/pMHC interface is surprising precise and extraordinarily malleable. We have seen that seemingly minor changes in the TCR/pMHC interface can abrogate function, as well as substantial conformational changes before and after TCR docking. Our understanding of T-cell biology has also been altered with the knowledge that MHC molecules can bind not only peptides, but also an array of natural and synthetic compounds. Here, we review some examples of the precision and flexibility intrinsic to the TCR/p/MHCI axis.

Original languageEnglish
Pages (from-to)433 - 441
Number of pages9
JournalImmunology and Cell Biology
Issue number5
Publication statusPublished - 28 May 2015

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