Clonal analysis of alloreactive T cell responses against the closely related B*2705 and B*2703 subtypes. Implications for HLA-B27 association to spondyloarthropathy.

Abstract

Alloreactive responses against closely related HLA-B27 subtypes were compared at the clonal level by fine specificity analysis of anti-B*2705 and anti-B*2703 CTL clones from unrelated HLA-B27- individuals with target cells expressing B*2701 to B*2706, and other HLA Ags. T cell epitope sharing between B*2705 and other subtypes was B*2705 > B*2703 > B*2702 > B*2701 > B*2704 > B*2706, and correlated with their amino acid differences. This suggests that identical or similar peptides, or peptide motifs, can be presented by multiple HLA-B27 subtypes to T cells, a feature that may be critical for the similar linkage of several subtypes to spondyloarthropathies. Other cross-reactions were predominantly with HLA-B61 and HLA-B60. Marked differences were observed in the nature and frequency of clonal reaction patterns among individuals. They correlated with structural features of the HLA-B Ags from each donor, suggesting that anti-HLA-B27 T cell responses are partially determined by the HLA-B phenotype of the responder. Ability to respond to particular HLA-B27-associated epitopes may determine differences in disease susceptibility among HLA-B27+ individuals. The anti-B*2703 and anti-B*2705 responses in the same individual were different. A major feature of anti-B*2703 CTL was that a large majority cross-reacted with B*2705. This can be explained by the effect of the single amino acid change in B*2703 on peptide binding and suggests that the B*2703-bound peptide repertoire is mainly a subset of that bound to B*2705, with few peptides being specifically presented by B*2703 to T cells.