Polymorphism in mitogenic effect of IgG1 monoclonal antibodies against T3 antigen on human T cells

It has recently been described that monoclonal antibody OKT 3, that reacts with the T3 determinant on all peripheral T lymphocytes in man, is also mitogenic for T cells. We have produced two monoclonal antibodies (WT 31 and WT 32) which apparently react with the T3 antigen. We have now tested the mitogenic effect of these antibodies and compared it with the mitogenicity of three other anti-T3 monoclonal antibodies, OKT 3, UCHT 1 (ref. 4) and anti-Leu 4 (ref. 5). Two distinct patterns were observed. WT 32 and OKT 3, both of the IgG2a subclass, were mitogenic for human T cells in all cases studied. By contrast, WT 31, UCHT 1 and anti-Leu 4, all of the IgG1 subclass, were devoid of mitogenic effect in 30% of the individuals tested (non-responders). The mitogenicity of all five anti-T3 antibodies was fully dependent on the presence of monocytes. Addition of purified monocytes from a responder to purified lymphocytes from a non-responder induced responsiveness to both IgG1 and IgG2a anti-T3 antibodies. These results suggest that the polymorphism in the mitogenic effect of these IgG1 antibodies is caused by polymorphism in monocyte function, possibly at the level of the Fc receptor that reacts with mouse IgG1.