Prediction of Peptide-MHC Binding Using Profiles

Prediction of peptide binding to major histocompatibility complex (MHC) molecules is a basis for anticipating T-cell epitopes. Peptides that bind to a given MHC molecule are related by sequence similarity. Therefore, a position-specific scoring matrix (PSSM)—also known as profile—derived from a set of aligned peptides known to bind to a given MHC molecule can be used as a predictor of both peptide–MHC binding and T-cell epitopes. In this approach, the binding potential of any peptide sequence (query) to the MHC molecule is determined by its similarity to a set of known peptide–MHC binders and can be obtained by comparing the query to the PSSM. Following structural considerations of the peptide–MHC interaction, we will describe here how to derive alignments and PSSMs that are suitable for the prediction of peptide–MHC binding.