Activation of lymphocytes by BAT and anti CTLA-4: comparison of binding to T and B cells.
In this study we compare the binding and immune stimulatory properties of BAT and anti CTLA-4 monoclonal antibodies (mAbs). Both antibodies were previously shown to manifest effective immune responses against tumor cells. We have described that BAT antibody, produced against Daudi, a B lymphoblastoid cell line, binds and activates T cells. In this paper we demonstrate that anti CTLA-4, produced against the T-cell activation determinant CTLA-4, binds also to B lymphoblastoid cell lines like Daudi and Raji. Both antibodies do not bind resting B cells. BAT binds resting T lymphocytes as well as activated T lymphocytes, whereas anti CTLA-4 binds only activated T cells. Competitive binding experiments indicate that the binding sites of BAT and anti CTLA-4 on activated T cells are distinct. We have studied the in vitro stimulatory effect of BAT and anti CTLA-4 on lymphocytes cultured with or without tumor cells. In contrast to BAT that increased the proliferation of lymphocytes that have been cultured with tumor cells, anti CTLA-4 did not synergize with tumor cells to enhance lymphocyte proliferation.
Raiter
A
A
Felsenstein Medical Research Center, Tel Aviv University Sackler School of Medicine, Rabin Medical Center, Petach Tikva, Israel.
Novogrodsky
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A
Hardy
B
B
D000069594:Abatacept; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000276:immunology* / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D001667:Binding, Competitive; D002051:Burkitt Lymphoma / Q000276:immunology / Q000473:pathology; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D006801:Humans; D018796:Immunoconjugates; D008213:Lymphocyte Activation / Q000187:drug effects*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept