T-cell allorecognition: a case of mistaken identity or deja vu?

Abstract

T cells bearing alphabeta T-cell receptors (TCRs) are selected by a subset of peptide-laden major histocompatibility (pMHC) molecules in the thymus and in the periphery and therefore are restricted to recognising host or 'self' MHC molecules. Nevertheless, T cells are inherently cross-reactive and often react with 'foreign' allogeneic MHC molecules (direct T-cell alloreactivity), manifested clinically as organ transplant rejection. Although the basis of T-cell alloreactivity has remained a puzzle to immunologists for decades, studies on alloreactive TCRs have begun to shed light on the basic mechanisms underpinning this 'mistaken identity'. Here we review recent advances in the field, focusi..