Comparison of rat and rat-mouse chimeric anti-murine CD4 antibodies in vitro. Chimeric antibodies lyse low-density CD4+ cells.
GK1.5, a rat anti-mouse CD4 mAb, is effective in the treatment of several autoimmune syndromes, induces tolerance to co-administered Ag, and prolongs allograft survival. We have constructed a family of molecules with GK1.5 V regions and mouse gamma 1, gamma 2a, gamma 2b, or gamma 3 constant regions to investigate the mechanisms underlying the effectiveness of GK1.5. The rat-mouse chimeric antibodies are specific for murine CD4 and have identical binding curves as rat GK1.5 on CD4+ T cells. The chimeric GK1.5 gamma 2a, GK1.5 gamma 2b, and GK1.5 gamma 3 antibodies are more efficient than rat GK1.5 at C-mediated cytotoxicity. This is attributed to the enhanced capacity of the chimeric antibodies, compared to rat GK1.5, to lyse CD4+ cells with a low cell surface Ag density. This observation may have important implications for therapy.
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Program in Cancer Biology, Stanford University School of Medicine, CA 94305.
Steinman
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000502:physiology*; D002460:Cell Line; D003165:Complement System Proteins; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis; D007958:Leukocyte Count; D051379:Mice; D051381:Rats; D011994:Recombinant Proteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000961:Antilymphocyte Serum; D000939:Epitopes; D011994:Recombinant Proteins; D003165:Complement System Proteins