Specificity of T-cell alloreactivity

T-cell alloreactivity is a well-established phenomenon, but its molecular basis has remained enigmatic. Although there are differences between T-cell recognition of conventional and allogeneic antigens, it has become increasingly clear that they share many similarities. Recent insights into the specificity of the T-cell receptor (TCR) for peptide and the seeming intrinsic affinity of the TCR for the surface of the MHC molecule have provided a better understanding of how the TCR and peptide-MHC complexes interact. Here, we highlight the similarities and differences between conventional and allogeneic recognition of TCR-peptide-MHC complexes, and discuss how our view of allorecognition has changed, as well as the implications for TCR specificity and T-cell development.