Activation of murine T cells by bacterial superantigens requires B7-mediated costimulation.
Staphylococcus enterotoxins bind class II MHC molecules on antigen-presenting cells (APC) and stimulate T cells expressing appropriate V beta gene products. Although the role of non-TcR-associated costimulatory receptors during antigen-specific T cell stimulation has been clearly established, the involvement of costimulatory activity in T cell activation by superantigens (SAgs) has been the matter of controversy. The aim of this study was to evaluate the role of the costimulatory-receptor ligand molecules CD28/B7 on bacterial SAg-mediated activation of naive murine T cells. We demonstrate in this report that a combination of monoclonal antibodies to murine B7.1 and B7.2 molecules inhibits the in vitro response of naive T cells to SAgs SEA, SEB, and TSST-1. The inhibition of T cell responses required simultaneous blocking of B7.1 and B7.2, suggesting that either B7.1 or B7.2 is sufficient to provide costimulatory signals to naive T cells in response to bacterial exotoxins. Inhibition of T cell activation by antibodies to B7-related molecules can be overcome by antibodies to CD28, a finding in agreement with the hypothesis that CD28-mediated signals participate in T cell activation by bacterial SAgs. These observations suggest that, as demonstrated for conventional antigen, T cell activation by SAgs requires the coordinated participation of TcR- and CD28-derived signals.
Muraille
E
E
Département de Biologie Moléculaire, Université Libre de Bruxelles, Belgium.
De Smedt
T
T
Thielemans
K
K
Urbain
J
J
Moser
M
M
Leo
O
O
D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology*; D001427:Bacterial Toxins / Q000276:immunology; D018106:CD28 Antigens / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018122:B7-1 Antigen; D001427:Bacterial Toxins; D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens