Structural analysis of (TCR—)HLA/peptide complexes: An initial study

Key to inducing adaptive immune responses is TCR recognition of HLA/peptide complexes, following HLA binding of the antigenic peptides. Numerous sequence-and structure-based predictors have been devised with regard to the recognition and the binding problem. The structure-based ones, however, are often not suited for high-throughput screenings of the greatly polymorphic immunogenic repertoire. It is then necessary to harvest simple yet discriminative structure-based features to be utilized prior to or in conjunction with some structure-based computational methods to help narrow down the search space. In this paper, bond lengths, bond angles, and torsion angles of the nonameric antigenic peptides bound by the HLA-A*0201 molecule are studied. Some consistent patterns were observed for φ and ψ torsions indicating that an antigenic peptide-already bound by the HLA-may be further recognized by the TCR when adoption of torsion angles that are of certain allowable values is favorable. A simple dichotomization rule was then established and applied successfully with 73.33% sensitivity, 75.55% specificity, and 74.44% accuracy.