AN IMMUNODOMINANT EPITOPE FROM MYCOBACTERIAL 65-KDA HEAT-SHOCK-PROTEIN PROTECTS AGAINST PRISTANE-INDUCED ARTHRITIS

Previous studies showed that mice with pristane-induced arthritis (PIA ) and those protected from the disease by preimmunization with mycobac terial 65-kDa heat shock protein (hsp65) possess raised immune respons es to hsp65. Additionally, T cells from hsp65-protected mice, but not from pristane-injected or normal mice, produced the Th2-associated cyt okines IL-4, IL-5, and IL-10 in response to stimulation with hsp65. He re we demonstrate that the specificity of the immune response to hsp65 and related heat shock protein (hsps) differs between protected and P IA mice. T cells from hsp65-protected mice respond to the bacterial hs ps tested but not to the mammalian homologue, hsp58. Similarly, they e xhibit high serum titers of anti-hsp65 Abs, yet they have virtually un detectable levels of anti-hsp58 IgG, By contrast, both cellular and hu moral immune responses are detectable to bacterial and mammalian hsps in mice with PIA. An immunodominant T cell epitope has been identified in hsp65-protected mice corresponding to amino acids 261-271 from hsp 65, Immunization of mice, either before or after the induction of arth ritis, with this bacterial peptide, but not its mammalian homologue, p rotects mice from the development of PIA, and protection is associated with the production of Th2-type cytokines. Other experiments revealed that T cells primed with bacterial 261-271 or the mammalian homologue do not cross-react at the proliferative or cytokine level. These resu lts demonstrate that an hsp65 peptide-specific Th2 response confers pr otection from PIA but do not support the idea that protection is media ted by a cross-reaction with self hsp58 in the joints.