Superantigen-like properties of an antibody bispecific for MHC class II molecules and the V beta domain of the T cell antigen receptor.
A working model for the action of superantigens (SAg) is that they are simple proteins having binding sites for both MHC class II molecules and the V beta domain of the TCR. Binding of a SAg to both molecules cross-links the TCR, inducing a biologic response. In this study, we have tested this working model using a SAg mimic consisting of a hybrid Ab bispecific for the murine MHC class II molecule I-E and the V beta 8 domain of the murine TCR. The bispecific Ab activates V beta 8-bearing T cells only in the presence of I-E molecules on APC when tested in vitro. The effect of the bispecific Ab in vivo revealed both clonal deletion and a reduction in the responsiveness of V beta 8-bearing T cells. Thus, the results suggest that molecules distinct from SAg that can bind to both MHC class II molecules and the V beta domain of the TCR can mimic the biologic actions of a SAg.
Yagi
J
J
Department of Microbiology and Immunology, Tokyo Women's Medical College, Japan.
Nakata
M
M
Uchiyama
T
T
Nishikawa
M
M
Mizushima
Y
Y
Nishioka
K
K
Ito
K
K
Yagita
H
H
Okumura
K
K
Janeway
C A
CA
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology*; D017637:Clonal Deletion; D004306:Dose-Response Relationship, Immunologic; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018033:Antibodies, Bispecific; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens