Binding of peptides naturally presented by HLA-B27 to the differentially disease-associated B*2704 and B*2706 subtypes, and to mutants mimicking their polymorphism

Abstract

B*2704 and B*2706 are closely related HLA-B27 subtypes of which the former but not the latter is associated to ankylosing spondylitis. Their peptide specificity relative to other disease-associated subtypes was analyzed by testing binding of self-peptides naturally presented by B*2705 or B*2702, and synthetic analogs, to B*2704, B*2706, and site-specific mutants mimicking their changes. Peptides with basic, aliphatic or aromatic C-terminal residues bound to B*2705 with similar affinity. In B*2704 C-terminal aliphatic/aromatic residues were preferred. B*2706 discriminated drastically between polar and nonpolar C-terminal residues, showing strong preference for Leu and Phe, and less than B*270..