HEAT-SHOCK PROTEINS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE) .1. IMMUNIZATION WITH A PEPTIDE OF THE MYELIN PROTEIN-2',3' CYCLIC-NUCLEOTIDE 3'-PHOSPHODIESTERASE THAT IS CROSS-REACTIVE WITH A HEAT-SHOCK PROTEIN ALTERS THE COURSE OF EAE

We describe sequence similarity and immunologic cross-reactivity betwe en a peptide of the mycobacterial hsp, HSP65, and the myelin protein 2 ',3' cyclic nucleotide 3' phosphodiesterase (CNP), We demonstrate that immunization with the homologous crossreactive CNP peptide (hsp-CNP p eptide) has significant biological consequences, Rats immunized with h sp-CNP peptide in either complete Freund's adjuvant (CFA) or incomplet e Freund's adjuvant (IPA) produce large amounts of peptide-specific an tibody, Isotypes of antibodies in animals immunized with peptide in CF A are IgG1 and IgG2a. Isotypes of antibodies in rats immunized with pe ptide in IFA are predominantly IgG1, with low titers of IgG2a. T cell proliferative responses to HSP65 are present in rats immunized with pe ptide in CPA, T cell responses to HSP65 initially are absent in rats i mmunized with peptide in IFA but develop over time, T cell proliferati ve responses to hsp-CNP peptide were not detected, None of the groups of rats developed clinical or histologic evidence of experimental auto immune encephalomyelitis (EAE), To induce EAE, rats preimmunized with hsp-CNP peptide were challenged with guinea pig spinal cord (GPSC) emu lsified in CFA, Rats preimmunized with peptide in CFA developed severe EAE. Rats preimmunized with hsp-CNP peptide in IFA were protected fro m EAE, with both a lower incidence and severity of disease, Injecting the murine monoclonal antibody recognizing the shared HSP65 and CNP ep itope did not protect against EAE. Our data suggest that a Th2 pattern of immune response to a CNP peptide that itself is non-encephalitogen ic protects against EAE, Immune responses to either hsp or myelin prot eins cross-reactive with hsp may play an important role in the develop ment of EAE. (C) 1996 Wiley-Liss, Inc.