Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies

doi:10.1084/jem.166.5.1351

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Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies

M Bruggemann, GT Williams, CI Bindon, MR Clark, MR Walker, R Jefferis, H Waldmann and MS Neuberger
Department of Pathology, Addenbrooke's Hospital, Cambridge, United Kingdom.

Cell lines have been established that secrete a matched set of human chimeric IgM, IgG1, IgG2, IgG3, IgG4, IgE, and IgA2 antibodies that are directed against the hapten 4-hydroxy-3-nitrophenacetyl. These chimeric antibodies secreted from mouse plasmacytoma cells behave exactly like their authentic human counterparts in SDS-PAGE analysis, binding to protein A and in a wide range of serological assays. The antibodies have been compared in their ability to bind human C1q as well as in their efficacy in mediating lysis of human erythrocytes in the presence of human complement. A major conclusion to emerge is that whereas IgG3 bound C1q better than did IgG1, the chimeric IgG1 was much more effective than all the other IgG subclasses in complement-dependent hemolysis. The IgG1 antibody was also the most effective in mediating antibody-dependent cell-mediated cytotoxicity using both human effector and human target cells. These results suggest that IgG1 might be the favoured IgG subclass for therapeutic applications.
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