Method, computing routine, device for predicting properties of MHC/peptide complexes, and data and peptides produced therefrom.

A method for producing an immunogenic peptide comprising an MHC class I or class II restricted T cell epitope that binds to an MHC class I or class II molecule and induces an MHC class I or II-restricted cytotoxic T cell response, said method comprising the steps of:

• (a) providing an amino acid sequence of a polypeptide of interest;
• (b) preparing one or more overlapping putative immunogenic peptide fragments of said polypeptide of interest;
• (c) receiving a representation of a complete or partial three-dimensional structure of said MHC class I or class II molecule;
• (d) obtaining an ensemble of conformational representations of peptide backbone structures of said putative immunogenic peptides, said conformational representations located within the binding site of said MHC molecule;
• (e) modeling the side chains of said peptide backbone structures of said ensemble in relation to said MHC molecule, thereby obtaining an ensemble of modeled MHC/peptide complexes;
• (f) evaluating the binding properties of said putative immunogenic peptides for said MHC molecule, by using a scoring function which combines at least:
• f1) average binding energy component obtained by evaluating one or more components of the potential energy of each complex of the ensemble of step (e);
• f2) conformational entropy component obtained by evaluating the conformational entropy for the complete ensemble of each modeled MHC/peptide complex of step (e);
• (g) inferring from the results obtained in (f), one or more putative immunogenic peptides that bind to said MHC molecule;
• (h) optionally preparing one or more of said putative immunogenic peptides of said polypeptide of interest;
• (i) optionally testing complexes of said one or more putative immunogenic peptides said MHC molecule for an ability to be recognized by a MHC cytotoxic T cells, and to thereby induce a cytotoxic T cell response to the epitope;
• and
• (e) selecting said one or more putative immunogenic fragments comprising an MHC class I or class II binding site that induce an MHC class I or class II cytotoxic T cell response to the epitope.