Epitope Specificity and T Cell Receptor Usage in Type II Collagen Induced Autoimmune Ear Disease

An immune response directed against type II collagen (CII) has been reported in several autoimmune diseases including the animal models of collagen-induced arthritis (CIA) and collagen-induced autoimmune ear disease (CIAED). In this communication, we have found that T cells from type II collagen-immunized DBA/1-lac could transfer auricular chondritis to naive mice. The T cells from type II collagen-immunized H-2r and H-2q mice recognize different epitopes from the CB11 peptide of CII. The CII-specific T cells from H-2Q background mice recognize peptide residues p121-147 (P1) but do not respond to residues p211-247 (P2). The T cells of H-2r mice immunized with CII respond better to P2 rather than P1. By altering certain amino acids within these epitopes, the response of CII-specific TCR to antigen has been increased or abolished. Our results suggest that the lysine residues at positions 129, 141, and 147 in P1, the arginine residue at position 227, and glutamic acid at position 230 in P2 might play an important role in the molecular interaction. Ten clonally distinct T cell hybridomas specific for CII have been established from H-2r B10.RIII mice and the β chains of their TCR have been analyzed. Three subfamilies, Vβ1, Vβ6, and Vβ8, were utilized with dominant expression of Vβ8 (60%). This is quite similar to the pattern found in type II collagen-induced arthritis in H-2q mice. This preferential use of Vβ8 in CIAED implies that an immunotherapy may make it possible to control this autoimmune disease, even in a MHC-diverse situation.