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) V pa and V-beta(c) haplotypes were derived to examine the influence of T CR 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 sugge sted alternative hypotheses. Thus, analysis of TCR V-beta congenic mic e allows for direct examination of V-beta genotypes in CIA control. Af ter immunization with bovine type II collagen, B10.Q-V-beta(a) mice sh owed no difference in arthritis susceptibility, onset, or severity whe n compared with prototype B10.Q mice. In contrast, B10.Q-V-beta(c) mic e, 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 o f V(beta)6(+) T cells in B10.Q-V-beta(a) mice significantly delayed ar thritis onset suggesting that, among those V-beta genes present in Vpa but absent in V-beta(c), V(beta)6(+) T cells contribute to arthritoge nesis. Our findings show that, in B10.Q-V-beta congenic mice, while th e V-beta(a) genotype does not prevent CIA, the highly truncated V-beta (c) genotype renders B10.Q mice resistant to CIA. Thus, deletions with in the V-beta TCR genome can indeed influence CIA and suggests that th e TCR repertoire displays only marginal flexibility in response to art hritogenic stimuli.