B10.Q (H-2q) mice congenic for the truncated T cell receptor (TCR) Vβa and Vβc haplotypes were derived to examine the influence of TCR Vβ enomic deletions in murine collagen-induced arthritis (CIA). Previous studies using gene complementation and segregation analyses suggested that in SWR (H-2q) mice, possession of the Vβa gene deletion results in CIA resistance. However, other studies have suggested alternative hypotheses. Thus, analysis of TCR Vβ congenic mice allows for direct examination of Vβ genotypes in CIA control. After immunization with bovine type II collagen, B10.Q-Vβ3 mice showed no difference in arthritis susceptibility, onset, or severity when compared with prototype B10.Q mice. In contrast, B10.Q-Vβc mice, which lack the Vβ6, 15, 17, and 19 families in addition to the Vβa deletion, were highly resistant to CIA. In vivo depletion of Vβ6+ T cells in B10.Q-Vβa mice significantly delayed arthritis onset suggesting that, among those Vβ genes present in Vβa but absent in Vβc, Vβ6+ T cells contribute to arthritogenesis. Our findings show that, in B10.Q-Vβ congenic mice, while the Vβa genotype does not prevent CIA, the highly truncated Vβc genotype renders B10.Q mice resistant to CIA. Thus, deletions within the Vβ TCR genome can indeed influence CIA and suggests that the TCR repertoire displays only marginal flexibility in response to arthritogenic stimuli.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Experimental Medicine|
|State||Published - Aug 1 1994|
ASJC Scopus subject areas