DIFFERENCES IN PEPTIDE PRESENTATION BETWEEN B27 SUBTYPES - THE IMPORTANCE OF THE P1 SIDE-CHAIN IN MAINTAINING HIGH-AFFINITY PEPTIDE BINDINGTO B-ASTERISK-2703

Susceptibility to spondyloarthropathies is strongly associated with th e MHC class I molecule HLA-B27, and is hypothesized to result from the presentation of arthritogenic peptides. Subtypes of B27 that differ s tructurally but are disease-associated ought to be capable of presenti ng such peptides, while nondisease-associated subtypes would not. We d emonstrate that B2703, the predominant West African B27 subtype that may not predispose to disease, is not recognized by most B2705-allore active CTL, and does not efficiently present a known B2705-restricted influenza A nucleoprotein (NP) peptide. We show inefficient presentat ion is due to a reduced binding affinity of B2703 for the NP peptide. Furthermore, substituting Arg for the naturally occurring Ser at P1 o f the NP peptide, restores high affinity binding and efficient present ation by B2703. Our results suggest that B*2703 will bind and present efficiently only a subset of the peptides that bind to B2705, in par ticular those with Arg or Lys at P1. The apparent lack of disease in i ndividuals with B2703 may be due to an inability to bind and present putative arthritogenic peptides.