Differences in peptide presentation between B27 subtypes: the importance of the P1 side chain in maintaining high affinity peptide binding to B*2703.

Susceptibility to spondyloarthropathies is strongly associated with the MHC class I molecule HLA-B27, 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 B2703, the predominant West African B27 subtype that may not predispose to disease, is not recognized by most B2705-alloreactive CTL, and does not efficiently present a known B2705-restricted influenza A nucleoprotein (NP) peptide. We show inefficient presentation is due to a reduced binding affinity of B2703 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 B2703. Our results suggest that B2703 will bind and present efficiently only a subset of the peptides that bind to B2705, in particular those with Arg or Lys at P1. The apparent lack of disease in individuals with B2703 may be due to an inability to bind and present putative arthritogenic peptides.