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The mechanism of synergistic complement‐mediated lysis of rat red cells by monoclonal IgG antibodies
Author(s) -
HughesJones Nevin C.,
Gorick Barbara D.,
Howard Jonathan C.
Publication year - 1983
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830130806
Subject(s) - isotype , lysis , antibody , monoclonal antibody , antigen , biology , microbiology and biotechnology , lytic cycle , cytolysis , immunology , biochemistry , cytotoxicity , in vitro , virus
Abstract The mechanism of synergistic complement‐mediated lysis of rat red cells was investigated using rat monoclonal antibodies against class IR1A a antigens. The increased lytic activity when using two antibodies simultaneously is due to the increase in the number of activated C1 molecules on the cell surface and this results from (a) an increase in the number of binding sites for C1q, (b) an increase in the functional affinity constant for C1q binding and (c) an increase in the rate of activation of C1. Complete lysis of red cells was only achieved if one member of the synergistic pair was of the γ 2b isotype, and this isotype weas the only one to which binding of 125 I‐labeled C1q could be detected. A partial synergistic effect was seen using an F(ab′) 2 fragment of antibody. Increased uptake and activation of C1 probably results both from the presence of two antibodies attached to each antigen molecule and from the formation of antigen‐antibody catenars.