Abstract
Proteins of the Major Histocompatibility Complex (MHC) bind self and nonself peptide antigens or epitopes within the cell and present them at the cell surface for recognition by T cells. All Tβcell epitopes are MHC binders but not all MCH binders are Tβcell epitopes. The MHC class II proteins are extremely polymorphic. Polymorphic residues cluster in the peptideβbinding region and largely determine the MHCβs peptide selectivity. The peptide binding site on MHC class II proteins consist of five binding pockets. Using molecular docking, we have modelled the interactions between peptide and MHC class II proteins from locus DRB1. A combinatorial peptide library was generated by mutation of residues at peptide positions which correspond to binding pockets (so called anchor positions). The binding affinities were assessed using different scoring functions. The normalized scoring functions for each amino acid at each anchor position were used to construct quantitative matrices (QM) for MHC class II binding prediction. Models were validated by external test sets comprising 4540β
known binders. Eighty percent of the known binders are identified in the best predicted 15β% of all overlapping peptides, originating from one protein.