BUB BNJ (H-2(Q)) IS A TCR DELETION MUTANT MOUSE STRAIN (TCR V-BETA(A), KJ16(-)) THAT IS SUSCEPTIBLE TO TYPE-II COLLAGEN-INDUCED ARTHRITIS/

Type II collagen-induced arthritis (CIA) in mice is an animal model of autoimmune inflammatory arthritis. Arthritis is induced in susceptibl e strains of mice (H-2(q) and H-2(r)) after immunization with heterolo gous or autologous type II collagen in CFA. Induction of CIA is T cell dependent and a restricted usage of TCR V beta genes has been found i n the arthritic joints and lymph nodes of mice with CIA. However, gene s within the MHC are not the only determinants of susceptibility to CI A as SWR/j, AU/ssj (both H-2(q)) and RIIIS/J(H-2(r)) mice are resistan t to the induction of CIA. These strains of mice are TCR V beta chain genes deletion mutants (TCR V beta(a) and TCR V beta(c) haplotypes) an d it was hypothesized that these mice are resistant to CIA because of the absence of a particular set of V beta TCR genes that are genomical ly deleted in these strains of mice. We now show that BUB/BnJ mice (H- 2(q)) are T cell subsets deficient because of the genomic deletion of TCR V beta 5, 8, 9, 11, 12, and 13 sub-families. Our data demonstrate that despite the deficiency in T cell subsets from genomic deletion of TCR V beta genes, BUB mice are highly susceptible to the development of CIA. These results indicate that genomic deletion of certain TCR V beta genes alone is not in itself sufficient to confer resistance to C IA. These results further suggest that other unknown gene(s) must also contribute to the induction of CIA.