Prevention of adjuvant arthritis in rats by a nonapeptide from the 65-kD mycobacterial heat shock protein: specificity and mechanism.
In a previous study we have shown that Lewis rats were completely protected from adjuvant arthritis by pretreatment with a nonapeptide (residues 180-188) of the 65-kD mycobacterial heat shock protein. Here we address questions of specificity and mechanism(s) of protection. We demonstrate that complete protection against adjuvant arthritis can only be achieved by pre-immunization with the nonapeptide, while pretreatment with either the octapeptide (residues 181-188) of the 65-kD heat shock protein or unrelated immunogenic peptides failed to affect adjuvant arthritis. Interestingly, pretreatment with the nonapeptide of the 65-kD heat shock protein did not protect Lewis rats from type II collagen-induced arthritis. These results demonstrate that protection is both epitope and disease specific. Co-injection of the nonapeptide with mycobacterial antigen even at a weight ratio of 5:1 (nonapeptide:mycobacteria) failed to influence the disease, suggesting that the role of the nonapeptide is not as a 'blocking peptide'. T cells from rats immunized with nonapeptide respond to the nonapeptide as well as to mycobacteria in vitro, and adoptively transfer protection to naive recipients. The data indicate that the nonapeptide-induced protection may result from a T cell-mediated specific suppression.
Yang
X D
XD
Research Department, Ciba-Geigy, Basle, Switzerland.
Gasser
J
J
Feige
U
U
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000517:prevention & control*; D000939:Epitopes; D006360:Heat-Shock Proteins / Q000276:immunology*; D007114:Immunization; D008297:Male; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D006360:Heat-Shock Proteins; D010446:Peptide Fragments