CHARACTERIZATION OF THE T-CELL RECEPTOR REPERTOIRE CAUSING COLLAGEN ARTHRITIS IN MICE

Collagen type II-induced arthritis (CIA) is generated in susceptible rodent strains by intradermal injections of homologous or heterologous native type II collagen in complete Freund's adjuvant. Symptoms of CIA are analogous to those of the human autoimmune disease, rheumatoid arthritis. CIA is a model system for T cell-mediated autoimmune disease. To study the T cell receptor (TCR) repertoire of bovine type II-specific T cells that may be involved in the pathogenesis of CIA in DBA/1Lac.J (H-2q) mice, 13 clonally distinct T cell hybridomas specific for bovine type II collagen have been established and the alpha and beta chains of their TCRs have been analyzed. These T cell hybridomas recognize epitopes that are shared by type II collagens from distinct species and not by type I collagens, and exhibit a highly restricted TCR-alpha/beta repertoire. The alpha chains of the TCRs employ three Valpha gene subfamilies (Valpha11, Valpha8, and Valpha22) and four Jalpha gene segments (Jalpha42, Jalpha24, Jalpha37, and Jalpha32). The Valpha22 is a newly identified subfamily consisting of approximately four to six members, and exhibits a high degree of polymorphism among four mouse strains of distinct Valpha haplotypes. In addition, the beta chains of the TCRs employ three Vbeta gene subfamilies (Vbeta8, Vbeta1, and Vbeta6), however the Vbeta8.2 gene segment is preferentially utilized (58.3%). In contrast, the Jbeta gene segment usage is more heterogeneous. On the basis of the highly limited TCR-alpha/beta repertoire of the TCRs of the panel of bovine type II-specific T cell hybrid clones, a significant reduction (60%) of the incidence of arthritis in DBA/1Lac.J mice is accomplished by the use of anti-Vbeta8.2 antibody therapy.