B-CELL AND T-CELL AUTOANTIGENS IN PRISTANE-INDUCED ARTHRITIS

Pristane-induced arthritis (PIA) is a murine disease resembling rheuma toid arthritis (RA) which is characterized by autoimmune responses to joint tissues. To identify the range of potential antigens targeted in PIA, proteins from arthritic or normal joint extracts were fractionat ed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS- PAGE) and systematically screened for the ability to react with either serum IgG, or cultured splenic T cells, obtained from healthy or arth ritic mice. Extracts from both normal and arthritic animals contained multiple proteins that were capable of reacting with murine serum IgG in immunoblotting experiments. In healthy controls, more bands were id entified in extracts prepared from 30-week-old mice than from 8-week-o ld animals, but the widest range of proteins bound were derived from a rthritic joints. Furthermore, the sera from PIA-positive mice reacted with more bands from each of the extracts than did normal sera. Fracti onated extracts prepared from healthy joints failed to stimulate the i ii vitro proliferation of splenic T cells from either normal or arthri tic animals. When arthritic joint components were screened, T cells fr om healthy mice responded weakly to some fractions, but multiple fract ions elicited strong proliferation by T cells From mice with PIA. A ba nd of apparent molecular mass 60000 was the protein most commonly boun d by serum Ige from arthritic mice, and the corresponding fraction sti mulated the highest responses by T cells from PIA-positive animals. Th ese results are consistent with the notion that the 60000 MW mammalian heat-shock protein is an important antigen in PIA, but that the autoi mmune response diversifies with the development of arthritis to target multiple joint components.