SUSCEPTIBILITY TO ANKYLOSING-SPONDYLITIS CORRELATES WITH THE C-TERMINAL RESIDUE OF PEPTIDES PRESENTED BY VARIOUS HLA-B27 SUBTYPES

Susceptibility to spondyloarthropaties is strongly associated with som e HLA-B27 alleles. Evidence suggests a direct pathogenic role for the B27 molecules which possibly present an arthritogenic peptide to the T cells. If this hypothesis is true, B27 subtypes that differ structura lly but are disease-associated ought to be capable of presenting such peptide(s), while non-disease-associated ones would not. We have recen tly described a B27 subtype, B2709, and shown its absence in ankylosi ng spondylitis (AS) patients. Here, we show the elution and sequence o f peptides from HLA-B2709 molecules. Similar to other B27 subtypes, t hese peptides are mainly nonamers with an Arg at position P2. Comparis on of the C-terminal anchors of peptides eluted from B2702 and B*2705 with those eluted from B2709 reveals that, while B*2702 and B*2705 h ave a broader specificity, B2709 molecules appear to only accept C-te rminal hydrophobic residues. A common feature shared by the two caucas oid AS-associated subtypes (B2702 and B*2705) but different from B*27 09, is the presence of a Tyr as peptide C-terminal anchor. The substit ution of Val for Tyr at the C terminus in one of the eluted peptides g reatly reduces the binding to B2709 molecules. This finding suggests Tyr as a discriminative amino acid allowed at the C terminus of peptid es bound to the AS-associated B27 subtypes, but not to those which are not associated with AS.