Analysis of the mouse T cell receptor (TCR) Vβ genome has revealed the existence of two distinct genotypes which bear deletions of certain Vβ genes. Mice bearing the Vaβ genotype lack approximately 50% of the Vβ genome while Vcβ mice lack 70% of the known Vβ genes. Studies of the experimental model collagen induced arthritis (CIA) have indirectly suggested that the presence of truncated Vβ genotypes may influence susceptibility to this autoimmune disease. In order to confirm the influence of Vaβ and Vcβ genotypes on CIA, we derived mice congenic for the known Vβ haplotypes in the CIA susceptible B10.RIII (H-2r) background. Flow cytometric analysis of splenic lymphocytes revealed normal T cell levels in both B10.RIII-Vβ congenic lines. Expectedly, a generalized increase in the expression of some non-deleted Vβ genes was detected. In addition, the mice were immunized with porcine type II collagen and monitored for CIA. B10.RIII-Vaβ mice showed little difference in arthritis incidence or severity versus B10.RIII, but a significant delay in the onset of CIA was seen. In contrast, B10.RIII-Vcβ mice showed a marked decrease in arthritis incidence versus B10.RIII and the severity of CIA in arthritic mice was also significantly lower (p < 0.01). Thus, in the B10.RIII strain, the presence of truncated TCR Vβ genotypes alters the development of CIA. These findings may shed light on the influence of TCR genotypes in the induction and development of human rheumatoid arthritis.
- CIA, collagen induced arthritis
- CII, native type II collagen
ASJC Scopus subject areas
- Immunology and Allergy