Analysis of the different subpeptidomes presented by the HLA class I molecules of the B7 supertype

MHC-I molecules of the HLA-B7 supertype preferentially bind peptides with proline at position 2. HLA-B*51:01 and B*51:08 present two predominant subpeptidomes, one with Pro2 and hydrophobic residues at P1, and another with Ala2 and Asp enriched at position 1. Here, we present a meta-analysis of the peptidomes presented by molecules of the B7 supertype to investigate the presence of subpeptidomes across different allotypes. Several allotypes presented subpeptidomes differing in the presence of Pro or another residue at P2. The Ala2 sub-peptidomes preferred Asp1 except in HLA-B*54:01, where ligands with Ala2 contained Glu1. Sequence align-ment and the analysis of crystal structures allowed us to propose positions 45 and 67 of the MHC heavy chain as relevant for the presence of subpeptidomes. Deciphering the principles behind the presence of subpeptidomes could improve our understanding of antigen presentation in other MHC-I molecules.Running title: HLA-B7 supertype subpeptidomes.