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.