Treatment of adjuvant arthritis in rats: vaccination potential of a synthetic nonapeptide from the 65 kDa heat shock protein of mycobacteria.

Adjuvant arthritis induced by mycobacteria in rats is a widely used model of chronic arthritis. A previously described nonapeptide (Thr-Phe-Gly-Leu-Gln-Leu-Glu-Leu-Thr, amino acid sequence 180-188) from the recombinant 65 kDa heat shock protein of Mycobacterium bovis BCG, which was found to contain a T-cell epitope recognized by both arthritogenic and protective T-cell clones in vitro, has been investigated for its vaccination and therapeutic potential in adjuvant arthritis in rats. The nonapeptide was found not to be arthritogenic, although the T cells from nonapeptide immunized rats cross-react in vitro with mycobacterial antigens. Intraperitoneal administration of 0.1 mg nonapeptide in oil at day -20 or days -2, -1 and 0, resulted in a marked reduction of incidence and severity of adjuvant arthritis. The disease process and severity were also influenced by therapeutic treatment with 0.1 mg nonapeptide injected intraperitoneally at days 7 to 10. Interestingly, subplantar or intravenous application of the nonapeptide had no influence on the disease process. Deletion of the N-terminal threonine led to complete loss of in vivo activity of the nonapeptide.