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.
Yang
X D
XD
Research Department, Ciba-Geigy Ltd, Basle, Switzerland.
Gasser
J
J
Riniker
B
B
Feige
U
U
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001168:Arthritis / Q000628:therapy*; D001169:Arthritis, Experimental / Q000517:prevention & control / Q000628:therapy*; D001426:Bacterial Proteins / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D007167:Immunotherapy; D007274:Injections, Intraperitoneal; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; C063820:SNP nonapeptide; C063821:SOP octapeptide