Functional characterization of a novel anti-B7 monoclonal antibody.
For optimal activation of T cells, binding of their T cell receptor to antigenic peptides in the context of major histocompatibility complex molecules on antigen-presenting cells (APC) is not sufficient. Accessory signals, provided by accessory cells, are needed to induce proliferation and clonal expansion of normal T cells. It has been shown previously that the B7 molecule, present on the cell surface of activated APC, can provide the second signal by binding to the CD28 molecule on T cells. Here we describe a novel anti-B7 (mAb), B7-24. This mAb binds to a functionally important epitope of the B7 molecule. Fab fragments of B7-24 can almost completely block anti-CD3-induced, B7-dependent T cell proliferation when tested in a model system where purified T cells are co-cultured with 3T6 cells expressing the human Fc gamma RII and human B7, in the presence of anti-CD3 mAb. In contrast, mAb B7-24 is not able to inhibit T cell proliferation in primary mixed lymphocyte reactions where purified T cells are co-cultured with Epstein-Barr virus-transformed B cells. These findings suggest that other cell surface molecules allow for maximal proliferation of T cells in mixed lymphocyte reactions, even when the interaction between B7 and CD28 is blocked by B7-24.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018122:B7-1 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex