Identification of T-cell receptor V beta deletion mutant mouse strain AU/ssJ (H-2q) which is resistant to collagen-induced arthritis.

ABSTRACT

Our laboratory is involved in investigating the role of T-cell receptor (Tcr) in collagen-induced arthritis (CIA). During these studies we found AU/ssJ (H-2q) mice to be resistant to CIA like SWR (H-2q), as compared with other H-2q strains with wild-type Tcr like DBA/1 and B10.Q. Upon screening with monoclonal antibodies F23.1 and KJ23a, AU/ssJ was found to be F23.1 negative (V beta 8 Tcr negative) and KJ23a positive (V beta 17a Tcr positive). Southern blot analysis on liver DNA using specific Tcr-V beta probes confirmed the deletion of V beta 8 gene family and also showed that AU/ssJ mice have deletions of V beta 9, V beta 13, V beta 12, and V beta 11 genes of Tcr. Further, these mice show a restriction fragment length polymorphism pattern with V beta 10, V beta 6, and V beta 17 probes similar to SWR mice as compared with B10 mice. Since SWR and AU/ssJ are from different backgrounds, these studies indicate that specific variable region beta chain genes of Tcr are crucial for susceptibility to CIA in mice. Furthermore, these studies identify an additional inbred strain which has also deleted 50% of its Tcr-V beta genes.