Major histocompatibility complex (MHC) restriction is a fundamental tenet of T cell biology, but the underlying mechanisms have remained controversial. The extent to which T cell receptors (TCRs) are biased towards MHC proteins in particular has been widely discussed. In a recent paper, Sharon et al. report direct evidence for coevolution between TCR and MHC genes, helping to explain how MHC compatibility and bias can be encoded within TCRs.
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