HLA-B27 (B*2701) specificity for peptides lacking Arg2 is determined by polymorphism outside the B pocket

Abstract

B*2701 differs from B*2705 by three amino acid changes: D → Y74, D → N77, L → A81, and from B*2702 only by two: D → Y74 and T → I80. Tyr74 is located in the C/F cavity of the peptide-binding site, and is unique to B*2701 among HLA-B27 subtypes. Binding of natural B*2705 and B*2702 ligands to B*2701, and to mutants mimicking subtype changes, was analyzed. In addition, sequencing of the peptides bound in vivo by B*2701 and the Y74 mutant was carried out. The main distinctive feature of B*2701 was its presentation of peptides with Gln2. Synthetic analogs bound in vitro similarly as the corresponding ligands with Arg2. Moreover, both Gln2 and Arg2 were dominant upon pool sequencing of B*2701-bou..