Lack of carboxyl-terminal tyrosine distinguishes the B*2706-bound peptide repertoire from those of B*2704 and other HLA-B27 subtypes associated with ankylosing spondylitis.
B*2704 and B*2706 are two closely related HLA-B27 subtypes, which differ from the common B*2705 by the Asp > Ser77, Val > Glu152, and Ala > Gly211 amino acid changes. In addition, B*2706 differs from B*2704 by the His > Asp114 and Asp > Tyr116 changes. In spite of their similarity B*2704, but not B*2706, was associated to ankylosing spondylitis in a same population. We have carried out pool sequence analyses of the peptides naturally bound to each of these subtypes, and of several individual peptide ligands. B*2704 and B*2706 shared with B*2705, among other features, their selectivity for Arg2 and their allowance for some aliphatic and aromatic C-terminal residues in their bound peptides. The main features that distinguished both subtypes from B*2705 were: 1) their failure to present peptides with C-terminal basic residues, and 2) their allowance for both polar and nonpolar residues at peptide position 3. A major difference between B*2704 and B*2706 was that C-terminal Tyr was prominent among the peptides bound to B*2704, but was not detected among those from B*2706. The use of Tyr as a C-terminal anchor motif is the only functional feature shared by the disease-associated B*2705, B*2702, and B*2704 subtypes that is absent in B*2706. This suggests that the ability of HLA-B27 to present peptides with C-terminal Tyr might be critical for its association to spondyloarthropathy.
García
F
F
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Facultad de Ciencias, Cantoblanco, Spain.
Marina
A
A
López de Castro
J A
JA
D000818:Animals; D017951:Antigen Presentation; D001665:Binding Sites; D002460:Cell Line; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013167:Spondylitis, Ankylosing / Q000276:immunology*; D014443:Tyrosine / Q000737:chemistry / Q000276:immunology*
D015796:HLA-B27 Antigen; D010455:Peptides; D014443:Tyrosine