SUMMARYHeat shock proteins (hsp) are immunodominant antigens in microbial infections. Previous work from this laboratory demonstrated that Yersinia-hsp60 (Y-hsp60)-reactive CD4 + ® ¯T cells play an important role for resolution of Y. enterocolitica infections in mice. In the present study we identified two epitopes of Y-hsp60 recognized by CD4 Th1 cell clones. The epitopes comprise 12 (214-225) and 13 (74-86) amino acid (aa) residues of Y-hsp60, and are the first described for MHC class II (I-A b ) molecules. Both epitopes are also recognized by T cells isolated from mesenteric lymph nodes from mice orogastrically infected with yersiniae. Stimulation of T cells with peptides of 12 and 13 aa residues of Y-hsp60 caused highly efficient proliferation compared with longer peptides, full-length recombinant Y-hsp60, or heatkilled Yersinia (HKY). Incubation of antigen-presenting cells with chloroquine blocked both peptide and HKY-triggered T cell proliferation, whereas cytochalasin B only blocked HKY-induced proliferation and to a lesser extent peptide-induced proliferation. The identified epitopes reside in a region of Yhsp60 that is conserved between Enterobacteriaceae but highly variable when compared with murine or human hsp60. Although both epitopes are identical to the related sequence of hsp60 (GroEL) of Escherichia coli, only weak T cell responses were observed upon stimulation with GroEL of E. coli, suggesting that other factors, e.g. flanking amino acid residues, might be important for antigen processing and T cell stimulation in a class II-restricted manner. Furthermore, these observations might be of significance for the rational design of subunit vaccines.

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