Understanding the complexity and malleability of T-cell recognition

Abstract

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 als..