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Sideways Killing: The Cytolysis of Fc Receptor‐Bearing Cells through Bridging to Cytolytic T Lymphocytes by Antibodies Specific for the T‐Cell Receptor‐T3 Complex
Author(s) -
ITO M.,
USUBA O.,
UNKELESS J. C.,
SCHREIBER R.,
CELADA F.,
BONA C. A.,
MORAN T. M.
Publication year - 1989
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1989.tb01170.x
Subject(s) - avidity , cytolysis , t cell receptor , antibody , biology , cd3 , t cell , microbiology and biotechnology , major histocompatibility complex , isotype , antigen , fc receptor , monoclonal antibody , immunology , virology , cytotoxic t cell , immune system , cd8 , in vitro , biochemistry
Cytolylic T lymphocytes (CTL) cause cytolysis of foreign or virus‐infected syngeneic cells when recognition of the target plus major histocompatibility complex (MHC) occurs via the T‐cell receptor (TCR). The recognition event leads to intimate contact between the two cells and activation of the cytolytic effector. Activation and target cell lysis can also occur in the presence of antibodies to the TCR. This is accomplished by bridging the effector cell TCR to the target cell FcR by an anti‐TCR monoclonal antibody (MoAb). Recent findings have placed the role of the FcR in this event in a questionable light. We confirm the importance of FcγR by demonstrating that: (a) melanoma cells are killed by CTL clones in the presence of anti‐TCR CD3 antibodies only when the melanoma cells express the FcγR on their surface; (b) native Ig, heat‐aggregated Ig, or an Fc fragment from an antibody expressing the same isotype as the anti‐TCR antibody can block the killing of high avidity FcγRI‐bearing cells mediated by anti‐TCR antibody (F23.1); and (c) anti‐FcγR MoAb (2.4G2)and a truncated soluble FcγRII molecule inhibit the killing of low‐avidity FcγRII‐bearing cells mediated by anti‐CD3 MoAb (145–2C11). Thus, we show that both high‐avidity FcγRI and low‐avidity FcγRII can mediate sideways killing depending upon the isotype of the anti‐TCR antibody and the type of FcR present on the target cell surface.