Why peptides? Their possible role in the evolution of MHC-restricted T-cell recognition

The peptide-presenting function of major histocompatibility complex (MHC) molecules permits pathogenic microorganisms to evade the host's immune system in two different ways: first, by escape of pathogen-derived antigenic peptides from presentation, and second, by molecular mimicry, that is resemblance between MHC-bound self and foreign peptides. These two mechanisms could have served as selective pressures in the evolution of the MHC. In this article, Zoltan Nagy and colleagues propose that escape from presentation selects for one or a few MHC molecules with the capacity to bind a broad range of different peptides. In contrast, molecular mimicry is considered to be the driving force for MHC diversification, that is it increases the number (polymorphism) and selectivity of peptide-binding sites.