COLLAGEN-INDUCED ARTHRITIS AND TCRS IN SWR AND B10.Q MICE EXPRESSING AN E(ALPHA)(K) TRANSGENE

B10.E(alpha)(k) transgenic mice were mated with H2-E(-) B10.Q and SWR mice. F-1 and F-1 x parental strain backcross progeny were tested for arthritis and autoimmune reactivity to mouse type II collagen (MII) af ter immunization with bovine, chick, deer, or human type II collagen. The results were correlated with the H-2 haplotype (b/q vs q/q) and th e TCR V beta profile of peripheral blood T cells in each mouse. Hybrid progeny expressed TCR profiles different from either parent because o f the TCR V beta genomic deletions of SWR mice (V beta(alpha)), the wi ld-type TCR allele of C57Bl/10 (B10) mice (V beta(b)), and the intrath ymic negative selection processes resulting from cell surface expressi on of E(alpha)(k)-A(beta)(q) or E(beta)(b)-E(alpha)(k) together with t he integrated retroviral genes Mtv-9 originating in B10 mice and Mtv-7 (Mls-1(a)) from SWR mice. (B10.E(alpha)(k) x SWR)F-1 mice developed hi gher IgG anti-MII Ab titers, but much milder arthritis than (B10.E x B 10.Q)F-1 mice. Expression of E(alpha)(k) did not change the level of I gG anti-MII Ab nor the degree of suspectibility to collagen-induced ar thritis (CIA) in the H-2(a/q) and H-2(b/q) progeny of (B10.E(alpha)(k) x Bu10.Q)F-1 x B10.Q matings, indicating that the Mtv-9-reactive, TCR V beta 5+, and V beta 11+ T cells are not critical to CIA. Among bovi ne type II collagen-immunized (B10.E(alpha)(k) x SWR)F-1 x SWR backcro ss mice: 1) arthritis severity is associated with the presence of V be ta(b) (p less than or equal to 0.01) and expression of E(alpha)(k) (p less than or equal to 0.05), but not with the MHC haplotype (b/q vs q/ q); 2) regression analysis showed a significant association (R = 0.99) between IgG anti-MII Ab titers and the level of Mtv-7-reactive V beta 6(+) T cells that was detectable in the IgG1, but not the IgG2a subcl ass. The data prompt the speculation that Mtv-7-reactive V beta 6(+) ( or V beta 7(+)) T cells in (B10.E(alpha)(k) x SWR)F-1 x SWR mice expre ss Th2-type properties, and thus contribute to the combination of mild arthritis but high anti-MII Ab titers that characterize mice of SWR h eritage.