Expression of an ovalbumin-specific V beta 8.2 TCR transgene inhibits collagen arthritis in B10.Q mice

Abstract

Previous studies have illustrated the importance of T cells bearing alpha beta TCRs in the induction and development of collagen induced arthritis (CIA) in mice. However, the scope of TCR usage in CIA has yet to be clearly defined. Given the inherent diversity of the TCR repertoire, the relative flexibility of the arthritogenic TCR repertoire specific for type II collagen (CII) is not clear. Therefore, we chose to examine the influence of a highly skewed TCR repertoire on CIA. Arthritis susceptible B10.Q (H-2q) mice were mated with C57L (H-2b) animals expressing an ovalbumin-specific V beta 8.2 TCR transgene (Tg) and Tg+ offspring were further backcrossed to B10.Q. Homozygous H-2q/q, V beta 8.2 Tg+ mice displayed a high level of V beta 8.2+ T cells in peripheral blood. However, expression of some endogenous V beta TCR, such as V beta 14, was still detected. Upon immunization with bovine CII in adjuvant, V beta 8.2 Tg+ mice were highly resistant to CIA when compared with Tg- littermates. Analysis of sera demonstrated a marked reduction in antibody specific for homologous mouse CII as well as heterologous bovine CII in Tg+ animals. Interestingly, V beta 8.2 Tg+ mice still mounted good antibody responses following immunization with human thyroglobulin, indicating that the skewed TCR repertoire affected anti-CII but not antithyroglobulin responses. Thus, our findings show that constraints placed on the TCR repertoire inhibit pathogenic responses against CII and suggest that in H-2q mice the arthritogenic TCR repertoire bears only limited flexibility.