COLLAGEN-INDUCED ARTHRITIS IN T-CELL RECEPTOR V-BETA CONGENIC B10.Q MICE

B10.Q (H-2(q)) mice congenic for the truncated T cell receptor (TCR) Vpa and V-beta(c) haplotypes were derived to examine the influence of TCR V-beta genomic deletions in murine collagen-induced arthritis (CIA). Previous studies using gene complementation and segregation analyses suggested that in SWR (H-2(q)) mice, possession of the V-beta(a) gene deletion results in CIA resistance. However, other studies have suggested alternative hypotheses. Thus, analysis of TCR V-beta congenic mice allows for direct examination of V-beta genotypes in CIA control. After immunization with bovine type II collagen, B10.Q-V-beta(a) mice showed no difference in arthritis susceptibility, onset, or severity when compared with prototype B10.Q mice. In contrast, B10.Q-V-beta(c) mice, which lack the V(beta)6, 15, 17, and 19 families in addition to the V-beta(a) deletion, were highly resistant to CIA. In vivo depletion of V(beta)6(+) T cells in B10.Q-V-beta(a) mice significantly delayed arthritis onset suggesting that, among those V-beta genes present in Vpa but absent in V-beta(c), V(beta)6(+) T cells contribute to arthritogenesis. Our findings show that, in B10.Q-V-beta congenic mice, while the V-beta(a) genotype does not prevent CIA, the highly truncated V-beta(c) genotype renders B10.Q mice resistant to CIA. Thus, deletions within the V-beta TCR genome can indeed influence CIA and suggests that the TCR repertoire displays only marginal flexibility in response to arthritogenic stimuli.