High T cell epitope sharing between two HLA-B27 subtypes (B*2705 and B*2709) differentially associated to ankylosing spondylitis

HLA-B*2705 is strongly associated with ankylosing spondylitis (AS) and reac tive arthritis. In contrast, B*2709 has been reported to be more weakly or not associated to AS. These two molecules differ by a single amino acid cha nge: aspartic acid in B*2705 or histidine in B*2709 at position 116, In thi s study, we analyzed the degree of T cell epitope sharing between the two s ubtypes. Ten allospecific T cell clones raised against B*2705, 10 clones ra ised against B*2703 but cross-reactive with B*2705, and 10 clones raised ag ainst B*2709 were examined for their capacity to lyse B"2705 and B*2709 tar get cells, The anti-B*2705 and anti-B*2703 CTL were peptide dependent as de monstrated by their failure to lyse TAP-deficient B*2705-T2 transfectant ce lls. Eight of the anti-B*2705 and five of the anti-B*2703 CTL clones lysed B"2709 targets, The degree of cross-reaction between B*2705 and B*2709 was donor dependent. In addition, the effect of the B"2709 mutation (D116H) on allorecognition was smaller than the effect of the other naturally occurrin g subtype change at this position, D116Y, These results demonstrate that B* 2705 and B*2709 are the antigenically closest HLA-B27 subtypes, Because all ospecific T cell recognition is peptide dependent, our results imply that t he B*2705- and B*2709-bound peptide repertoires are largely overlapping. Th us, to the extent to which linkage of HLA-B27 with AS is related to the pep tide-presenting properties of this molecule, our results would imply that p eptides within a relatively small fraction of the HLA-B27-bound peptide rep ertoire influence susceptibility to this disease.