T-cell receptor Vbeta deletion and Valpha polymorphism are responsible forthe resistance of SWR mouse to arthritis induction

Collagen type II-induced arthritis (CIA) develops in susceptible mouse stra ins after intradermal injections of type II collagen (CII) in complete Freu nd's adjuvant (CFA). Susceptibility to CIA in mice is linked to genes of th e major histocompatibility complex (MHC). Although the SWR mouse has a susc eptible MHC haplotype (H2(q)), it is resistant to CIA, SWR exhibits at leas t two known immunological defects: (1) it contains a germline deletion of a bout 50% of T-cell receptor (TCR) V beta-chain gene segments, and (2) SWR i s deficient in complement component C5. It has been shown that T cells that express TCRV alpha 11.1 and TCRV beta 8.2 play a substantial role in the p athogenesis of arthritis in the DBA/1 mouse (H2(q)). We generated SWR trans genic (tg) mice to determine whether the expression of pathogenic V alpha 1 1.1 and/or V beta 8.2 transgenes would confer arthritis susceptibility. Art hritis was induced in the SWR TCR alpha beta tg mice, but not in SWR TCR be ta tg mice. To address the role of V alpha 11.1 in arthritis susceptibility , we examined the allelic polymorphisms of the Tcra-V11-gene subfamily memb ers between the arthritis susceptible DBA/1 mouse and the arthritis-resista nt SWR mouse strain. The amino acid sequences of the V alpha 11.1 alleles d iffer at two positions (codons 18 and 68). Accordingly, these two amino aci d changes are sufficient to allow the production of pathogenic T cells in S WR mice. This is the first demonstration of the association of a particular Tcra-V allele and arthritis susceptibility in mice.