Multispecific CD4(+) T cell response to a single 12-mer epitope of the immunodominant heat-shock protein 60 of Yersinia enterocolitica in Yersinia-triggered reactive arthritis: Overlap with the B27-restricted CD8 epitope, functional properties, and epitope presentation by multiple DR alleles

Yersinia heat-shock protein 60 (Ye-hsp60) has recently been found to be a d ominant CD4 and CD8 T cell Ag in Yersinia-triggered reactive arthritis. The nature of this response with respect to the epitopes recognized and functi onal characteristics of the T cells is largely unknown. CD4(+) T cell clone s specific for Ye-hsp60 were raised from synovial fluid mononuclear cells f rom a patient with Yersinia-triggered reactive arthritis. and their specifi city was determined using three recombinant Ye-hsp60 fragments, overlapping 18-mer synthetic peptides as well as truncated peptides. Functional charac teristics were assessed by cytokine secretion analysis in culture supernata nts after specific antigenic stimulation. Amino acid positions relevant for T cell activation were detected by single alanine substitutions within the epitopes, Fragment LI comprising amino acid sequence 182-371 was recognize d by the majority of clones, All these clones were specific for peptide 319 -342, Th1 clones and IL-10-secreting clones occurred in parallel, sometimes with the same fine specificity. The 12-mer core epitope 322-333 is a degen erate MHC binder and is presented to some T cell clones in a "promiscuous" manner, This epitope is almost identical with a B27-restricted CTL epitope of Ye-hsp60. Cross-reactivity of Ye-hsp60-specific T cell clones with self- hsp60 was not observed. In conclusion, an interesting Ye-hsp60 T cell epito pe has been identified and characterized. It remains to be determined wheth er this epitope is also relevant in other reactive arthritis patients.