Antibody responses to mycobacterial and self heat shock protein 65 in autoimmune arthritis: epitope specificity and implication in pathogenesis.
Many autoimmune diseases are believed to involve primarily T cell-mediated effector mechanisms. There is increasing realization, however, that Abs may also play a vital role in the propagation of T cell-driven disorders. In this study, on the rat adjuvant-induced arthritis (AA) model of human rheumatoid arthritis, we examined the characteristics of serum Ab response to mycobacterial heat shock protein (hsp) 65 (Bhsp65), self (rat) hsp65 (Rhsp65), and linear peptides spanning these two molecules. The AA-resistant WKY (RT.1(l)) rat responded to the heat-killed Mycobacterium tuberculosis immunization with a rapid burst of Abs to both Bhsp65 and Rhsp65. These Abs reacted with numerous peptide epitopes; however, this response was reduced to a few epitopes with time. On the contrary, the susceptible Lewis (RT.1(l)) rat developed a relatively lower Ab response to Bhsp65, and Abs to Rhsp65 did not appear until the recovery from the disease. The Ab response in Lewis rats diversified with progression of AA, and there was an intriguing overlap between the repertoire of Bhsp65-reactive B and T cells during the recovery phase of AA. Nonetheless, subsets of the repertoire of the late Abs in both rat strains became focused on the same epitope regions of Bhsp65 and Rhsp65. The functional relevance of these Abs was evident from the results showing that sera from recovery phase Lewis or WKY rats, but not that of naive rats, afforded protection against subsequent AA. These results are of significance in further understanding of the role of humoral immunity in the pathogenesis of autoimmune arthritis.
Kim
Hong Ro
HR
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Kim
Eugene Y
EY
Cerny
Jan
J
Moudgil
Kamal D
KD
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000008:administration & dosage / Q000276:immunology*; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY
D000907:Antibodies, Bacterial; D001324:Autoantigens; D001426:Bacterial Proteins; D018834:Chaperonin 60; D000939:Epitopes; D010446:Peptide Fragments; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins