PROTECTIVE ROLE FOR HEAT-SHOCK PROTEIN-REACTIVE ALPHA-BETA T-CELLS INMURINE YERSINIOSIS

To investigate the role of heat shock proteins (HSP) of Yersinia enter ocolitica for the host immune response against this pathogen, we clone d and expressed a 60-kDa HSP of Y. enterocolitica serotype O8. A fragm ent of Y. enterocolitica O8 HSP60 encoded by amino acids 90 to 286 was sequenced and showed more than 90% homology with HSP60 of Y. enteroco litica O3 and GroEL of Escherichia coli and 59% homology with HSP65 of Mycobacterium bovis. The arthritogenic T-cell epitope of mycobacteria l HSP65 (amino acid residues 180 to 188) was not found on Yersinia HSP 60. To determine whether Yersinia HSP60 is an immunodominant antigen, the immune responses of Yersinia-infected C57BL/6 mice were analyzed. Yersinia-infected mice evolved a significant serum antibody and spleni c T-cell response against Yersinia HSP60. CD4(+) alpha beta T-cell cro nes which were generated from splenic T cells isolated from either Yer sinia-infected or Yersinia HSP60-immunized mice, recognized both heat- killed Yersinia serotypes O3 and O8 as well as recombinant Yersinia HS P60 but not heat-killed Yersinia pseudotuberculosis, Salmonella typhim urium, or recombinant HSP65 of Mycobacterium bovis. The adoptive trans fer of HSP60-reactive T-cell clones mediated significant protection ag ainst a lethal infection with Y. enterocolitica O8. These results indi cate that HSP60 of Y. enterocolitica is an immunodominant antigen whic h is recognized by both antibodies and CD4(+) alpha beta T cells. More over, this is the first report providing direct evidence that microbia l HSP may elicit a protective immune response which is not associated with autoimmunity.