T-Cell Receptors and Collagen Induced Arthritis in H-2RMice

Abstract

Mouse strains BIO, B10.RIII, RIIIS/J and the Fl and backcross progeny arising from them were tested for susceptibility to porcine type II collagen-induced arthritis (PII-CIA). The clinically severe arthritis of rapid onset that is characteristic of PII-immunized B10.RIII mice developed predominantly in hybrid offspring that had inherited at least one copy of wild type T cell receptor (TCR) genes (Vβ^b genotype) from the B10 or B10.RIII parent. The results indicate that, in the development of PII-CIA, mice expressing the H-2^r/r haplotype preferentially utilize TCR Vp genes that are normally encoded within the TCR Vβ genomic deletion region of RIIIS mice (Vβ^c). After aggressive immunization with PII, the use of alternative TCR Vβ genes, encoded outside of the RIIIS deletion region, produced a high IgG antibody response that was cross-reactive with mouse type II collagen (MII) and equivalent to that of B10.RIII mice, but only a very mild, late onset arthritis of 56% (27/48) incidence in RIIIS male mice and 28% (10/35) incidence in RIIIS female mice. In comparison, B10.RIII mice routinely developed early onset of PII-CIA of significantly higher incidence (100%; pa (a retroviral superantigen). and to homologous type II collagen is discussed.