B10.Q (H-2q) mice congenic for the truncated T cell receptor (TCR) Vβ2 and Vβc haplotypes were derived to examine the influence of TCR Vβgenomic 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 Vβ2 gene deletion results in CIA resistance. However, other studies have suggested alternative hypotheses. Thus, analysis of TCR Vβcongenic mice allows for direct examination of Vβgenotypes in CIA control. After immunization with bovine type II collagen, B10.Q-Vβ2 mice showed no difference in arthritis susceptibility, onset, or severity when compared with prototype B10.Q mice. In contrast, B10.QVβc mice, which lack the Vβ6, 15, 17, and 19 families in addition to the Vβ2 deletion, were highly resistant to CIA. In vivo depletion of Vβ6+ T cells in B10.Q-Vβ2 mice significantly delayed arthritis onset suggesting that, among those Vβgenes present in Vβ2 but absent in Vβc, Vβ6+ T cells contribute to arthritogenesis. Our findings show that, in B10.Q-Vβ congenic mice, while the Vβ2 genotype does not prevent CIA, the highly truncated Vβc genotype renders B10.Q mice resistant to CIA. Thus, deletions within the VβTCR genome can indeed influence CIA and suggests that the TCR repertoire displays only marginal flexibility in response to arthritogenic stimuli.
ASJC Scopus subject areas
- Immunology and Allergy