T-cell epitope prediction with combinatorial peptide libraries.

T cell receptors (TCR) recognize antigenic peptides in complex with the major histocompatibility complex (MHC) molecules and this trimolecular interaction initiates antigen-specific signaling pathways in the responding T lymphocytes. For the study of autoimmune diseases and vaccine development, it is important to identify peptides (epitopes) that can stimulate a given TCR. The use of combinatorial peptide libraries has recently been introduced as a powerful tool for this purpose. A combinatorial library of n-mer peptides is a set of complex mixtures each characterized by one position fixed to be a specified amino acid and all other positions randomized. A given TCR can be fingerprinted by screening a variety of combinatorial libraries using a proliferation assay. Here, we present statistical models for elucidating the recognition profile of a TCR using combinatorial library proliferation assay data and known MHC binding data.