T-CELL RECEPTORS AND COLLAGEN-INDUCED ARTHRITIS IN H-2R MICE

Mouse strains B10, B10.RIII, RIIIS/J and the F1 and backcross progeny arising from them were tested for susceptibility to porcine type 11 co llagen-induced arthritis (PII-CIA). The clinically severe arthritis of rapid onset that is characteristic of PII-immunized B 10.RIII mice de veloped predominantly in hybrid offspring that had inherited at least one copy of wild type T cell receptor (TCR) genes (Vbeta(b) genotype) from the B10 or BIO.RIII parent. The results indicate that, in the dev elopment of PII-CIA, mice expressing the H-2(r/r) haplotype preferenti ally utilize TCR Vbeta genes that are normally encoded within the TCR Vbeta genomic deletion region of RIIIS mice (Vbeta(c)). After aggressi ve immunization with PII, the use of alternative TCR Vbeta genes, enco ded outside of the RIIIS deletion region, produced a high IgG antibody response that was cross-reactive with mouse type II collagen (MII) an d equivalent to that of B 10.RIII mice, but only a very mild, late ons et arthritis of 56% (27/48) incidence in RIIIS male mice and 28% (10/3 5) incidence in RIIIS female mice. In comparison, B10.RIII mice routin ely developed early onset of PII-CIA of significantly higher incidence (100%; p<0.005) and four-fold greater severity, even after milder imm unization protocols. The data are compatible with the proposal that th e clinically weak CIA response of RIIIs mice may be primarily antibody driven while the severe CIA of B10.RIII mice reflects the added infla mmatory effects of collagen-reactive effector-T cells in the joint. Th e apparent concordance of TCR Vbeta utilization in the murine T cell r esponse to MAM (a superantigen produced by M. arthritis), to Mls-1a (a retroviral superantigen), and to homologous type II collagen is discu ssed.