Cross-reactivity in T-cell antigen recognition

The molecular interactions between the T-cell receptor (TCR) and peptide-MH C (pMHC) have been elucidated in recent years. Nevertheless, the fact that binding of only slightly different ligands by a TCR, or ligation of the sam e pMHC at different developmental stages of the T cell, can have opposing c onsequences, continues to pose intellectual challenges. Kinetic proofreadin g models, which have at their core the dissociation rates of pMHC from the TCR, are best suited to account for these observations. However, T cells ca n be triggered by peptides with often minimal homology to the primary immun ogenic peptide. This cross-reactivity of the TCR is manifest at several lev els, from positive selection of immature thymocytes to homeostasis and anti gen-cross-reactive immune responses of mature peripheral T cells. The impli cations of the high cross-reactivity of T-cell antigen recognition for self -tolerance and T-cell memory are discussed.