TY - JOUR
T1 - Induction of T cell proliferation with anti-CD3 switch-variant monoclonal antibodies: effects of heavy chain isotype in monocyte-dependent systems
AU - van Lier, R. A.
AU - Boot, J. H.
AU - de Groot, E. R.
AU - Aarden, L. A.
PY - 1987
Y1 - 1987
N2 - Monoclonal antibodies (mAb) directed against the CD3 (T3), antigen are able to induce proliferation in resting human T lymphocytes. T cell proliferation only occurs in the presence of monocytes that carry the proper Fc receptor for the mAb used. To further analyze the role of the Fc portion of anti-CD3 mAb in proliferation induction, we isolated, starting from a gamma 1 anti-CD3-producing hybridoma, four heavy-chain isotype switch-variant antibody-secreting clones, producing gamma 2b, gamma 2a, epsilon and alpha, respectively. All variant antibodies recognize the CD3 antigen as determined by immunoprecipitation and cross-blocking experiments. With this series of isotype variant antibodies we were able, in proliferation induction experiments, to confirm the Fc receptor polymorphism for murine IgG2a, IgG2b and IgG1 on human monocytes. Moreover, we found that all 30 donors tested responded to the IgE anti-CD3 antibody, while no IgA responders could be identified. The induction of proliferation by the IgE variant antibody does not require the 72-kDa Fc receptor which is responsible for the interaction with mouse IgG2a. Nonresponsiveness to the IgG1 antibody, but not to the IgG2b or IgA variant antibodies, could be overcome by the addition of exogenous interleukin 2 to the cultures. When the switch-variant antibodies were used to induce IgM synthesis in peripheral blood mononuclear cells only low IgM synthesis was found, with the exception of the IgE variant, which induced excellent T cell help for IgM production
AB - Monoclonal antibodies (mAb) directed against the CD3 (T3), antigen are able to induce proliferation in resting human T lymphocytes. T cell proliferation only occurs in the presence of monocytes that carry the proper Fc receptor for the mAb used. To further analyze the role of the Fc portion of anti-CD3 mAb in proliferation induction, we isolated, starting from a gamma 1 anti-CD3-producing hybridoma, four heavy-chain isotype switch-variant antibody-secreting clones, producing gamma 2b, gamma 2a, epsilon and alpha, respectively. All variant antibodies recognize the CD3 antigen as determined by immunoprecipitation and cross-blocking experiments. With this series of isotype variant antibodies we were able, in proliferation induction experiments, to confirm the Fc receptor polymorphism for murine IgG2a, IgG2b and IgG1 on human monocytes. Moreover, we found that all 30 donors tested responded to the IgE anti-CD3 antibody, while no IgA responders could be identified. The induction of proliferation by the IgE variant antibody does not require the 72-kDa Fc receptor which is responsible for the interaction with mouse IgG2a. Nonresponsiveness to the IgG1 antibody, but not to the IgG2b or IgA variant antibodies, could be overcome by the addition of exogenous interleukin 2 to the cultures. When the switch-variant antibodies were used to induce IgM synthesis in peripheral blood mononuclear cells only low IgM synthesis was found, with the exception of the IgE variant, which induced excellent T cell help for IgM production
U2 - https://doi.org/10.1002/eji.1830171112
DO - https://doi.org/10.1002/eji.1830171112
M3 - Article
C2 - 2960543
SN - 0014-2980
VL - 17
SP - 1599
EP - 1604
JO - European journal of immunology
JF - European journal of immunology
IS - 11
ER -