Differences in peptide presentation between B27 subtypes: The importance of the P1 side chain in maintaining high affinity peptide binding to B^{{black star}}2703

Susceptibility to spondyloarthropathies is strongly associated with the MHC class I molecule HLA-027, and is hypothesized to result from the presentation of arthritogenic peptides. Subtypes of B27 that differ structurally but are disease-associated ought to be capable of presenting such peptides, while nondisease-associated subtypes would not. We demonstrate that B^{{black star}}2703, the predominant West African B27 subtype that may not predispose to disease, is not recognized by most B^{{black star}}2705-alloreactive CTL, and does not efficiently present a known B^{{black star}}2705-restricted influenza A nucleoproteln (NP) peptide. We show Inefficient presentation is due to a reduced binding affinity of B^{{black star}}2703 for the NP peptide. Furthermore, substituting Arg for the naturally occurring Ser at P1 of the NP peptide, restores high affinity binding and efficient presentation by B^{{black star}}2703. Our results suggest that B^{{black star}}2703 will bind and present efficiently only a subset of the peptides that bind to B^{{black star}}2705, in particular those with Arg or Lys at P1. The apparent lack of disease In Individuals with B^{{black star}}2703 may be due to an inability to bind and present putative arthritogenic peptides.