INDUCTION OF ARTHRITIS IN BALB C MICE BY CARTILAGE LINK PROTEIN - INVOLVEMENT OF DISTINCT REGIONS RECOGNIZED BY T-LYMPHOCYTES AND B-LYMPHOCYTES/

Both type II collagen and the proteoglycan aggrecan are capable of ind ucing an erosive inflammatory polyarthritis in mice. In this study we provide the first demonstration that Link protein (LP), purified from bovine cartilage, can produce a persistent, erosive, inflammatory poly arthritis when injected repeatedly intraperitoneally into BALB/c mice. We discovered a single T-cell epitope, located within residues 266 to 290 of bovine LP (NDGAQIAKNGQI-FAAWKLLGYDRCD), which is recognized by bovine LP-specific T lymphocytes, We also identified three immunogeni c regions in bovine LP that contain epitopes recognized by antibodies in hyperimmunized sera. One of these B-cell regions is found in the mo st species-variable domain of LP (residues 1 to 36), whereas the other epitopes are located in the most conserved regions (residues 186 to 2 30 and 286 to 310), The latter two regions contain an AGWLSDGSVQYP mot h shared by the G1 globulin domain of aggrecan core protein, versican, neurocan, glial hyaluronan-binding protein, and the hyaluronan recept or CD44. Our data reveal that the induction of arthritis is associated with antibody reactivities to B-cell epitopes located at residues 1 t o 19, Together, these observations show that another cartilage protein , LP, Like type II collagen and the proteoglycan aggrecan, is capable of inducing an erosive inflammatory arthritis in mice and that the imm unity to LP involves recognition of both T- and B-cell epitopes, This immunity may be of importance in the pathogenesis of inflammatory join t diseases, such as juvenile rheumatoid arthritis, in which cellular i mmunity to LP has been demonstrated.