A mycobacterial 65-kD heat shock protein induces antigen-specific suppression of adjuvant arthritis, but is not itself arthritogenic.
A recombinant (r)65-kD protein from Mycobacterium leprae, at levels far in excess of those present in whole mycobacteria, was unable to induce arthritis. Even when combined with a synthetic adjuvant, CP20961, to mimic the peptidoglycan adjuvant component of the mycobacterial cell wall, the r65-kD protein failed to induce arthritis. Pretreatment with as little as 1 microgram r65-kD protein protected rats against arthritis induced by M. tuberculosis, but this r65-kD protein was markedly less able to protect against arthritis induced by the synthetic adjuvant, CP20961, or type II collagen. The r65-kD protein appears, therefore, to produce an antigen-specific protection against arthritis induced by bacterial cell walls containing the 65-kD protein. Such protection can be overcome, however, by arthritogenic T lymphocytes, suggesting that protection occurs by preventing clonal proliferation of autoreactive T lymphocytes that are induced by the adjuvant properties of mycobacterial cell walls. How the r65-kD protein abrogates this particular adjuvant activity, and the nature of the arthritogenic self antigen(s), remain to be elucidated.
Billingham
M E
ME
Connective Tissue Disease Research, Eli Lilly and Co., Windlesham, Surrey, United Kingdom.
Carney
S
S
Butler
R
R
Colston
M J
MJ
D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control; D003001:Cloning, Molecular; D003094:Collagen; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D008970:Molecular Weight; D009169:Mycobacterium tuberculosis / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology*
D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; D003094:Collagen