Insights from MHC-bound peptides

Cytotoxic T cells recognize short antigenic peptides, the processing products of protein antigens, when they are bound to major histocompatibility complex (MHC) class I molecules. Peptide binding to MHC molecules has been studied extensively in numerous laboratories, providing vast amounts of sequence and structure data that have been used as a rich source for bioinformatic research. MHC-bound peptides and their flanking sequences provide information about the sequence requirements of the different processing stages, in particular, the cleavage by the proteasome and the binding to MHC molecules. Elucidation of these sequence requirements sheds light on the evolutionary forces that have shaped and designed these peptides, and should lead to the development of an integrative predictive algorithm. Remarkably, the peptide sequence and structure data are also valuable for the study of biological questions that are apparently unrelated to cellular immunity, namely, sequence-structure relationship and genome annotation. Here we describe our computational analyses of MHC-bound peptides, applied to all these biological topics.