Dominant Role of the ERAP1 Polymorphism R528K in Shaping the HLA–B27 Peptidome Through Differential Processing Determined by Multiple Peptide Residues

Abstract

The R528K, but not the N575D/Q725R, polymorphism alters the expression levels of many HLA-B*27:05-bound peptides, depending on the susceptibility of their N-terminal residues to trimming and depending on the size of the amino acid side chains at multiple positions downstream of the N-terminus. The significant alterations in the B*27:05 peptidome and the structural features of the peptides that determine their differential expression in distinct ERAP1 contexts account for the association of the R528K polymorphism with AS.