Murine B7 antigen provides a sufficient costimulatory signal for antigen-specific and MHC-restricted T cell activation.
We have previously shown that the murine B7 (mB7) molecule, when expressed in Chinese hamster ovary cells in stable fashion, can costimulate with anti-CD3 mAb or Con A to induce T cell activation. We have now derived, by gene transfection, Chinese hamster ovary cell lines that express the I-Ad molecule, either alone or in context with mB7. We have analyzed these transfectants for their capacity to present Ag to murine CD4+ T lymphocytes. I-Ad/mB7-double transfectants were able to stimulate mixed lymphocyte reactions and to present peptide Ag to specific T cells. Chinese hamster ovary cells that expressed only the I-Ad molecule were not able to stimulate T cell proliferation in these systems. Thus, the mB7 protein is a sufficient costimulatory molecule for the physiologic, Ag-dependent/MHC-restricted activation of murine CD4+ T cells. Stimulation of T cell bulk cultures resulted predominantly in the production of IL-2 and not of IL-4. The costimulatory activity of mB7 is not, however, restricted to the IL-2-secreting subset. We have identified one IL-4-secreting T cell clone, CDC35, which is responsive to mB7 triggering. Finally, we present experiments that suggest that mB7 and peptide/MHC complexes need to be expressed on the same cell for optimal induction of T cell activation.
D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D000954:Antigens, Surface / Q000502:physiology*; D018122:B7-1 Antigen; D017252:CD3 Complex / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D006224:Cricetinae / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice / Q000235:genetics; D014162:Transfection
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018122:B7-1 Antigen; D017252:CD3 Complex; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D003208:Concanavalin A; D015847:Interleukin-4