In silico grouping of peptide/HLA class I complexes using structural interaction characteristics

Motivation: Classification of human leukocyte antigen (HLA) proteins into supertypes underpins the development of epitope-based vaccines with wide population coverage. Current methods for HLA supertype definition, based on common structural features of HLA proteins and/or their functional binding specificities, leave structural interaction characteristics among different HLA supertypes with antigenic peptides unexplored. Methods: We describe the use of structural interaction descriptors for the analysis of 68 peptide/HLA class I crystallographic structures. Interaction parameters computed include the number of intermolecular hydrogen bonds between each HLA protein and its corresponding bound peptide, solvent accessibility, gap volume and gap index. Results: The structural interactions patterns of peptide/HLA class I complexes investigated herein vary among individual alleles and may be grouped in a supertype dependent manner. Using the proposed methodology, eight HLA class I supertypes were defined based on existing experimental crystallographic structures which largely overlaps (77% consensus) with the definitions by binding motifs. This mode of classification, which considers conformational information of both peptide and HLA proteins, provides an alternative to the characterization of supertypes using either peptide or HLA protein information alone.