Activation of T lymphocytes by immobilized monoclonal antibodies to CD3: regulatory influences of monoclonal antibodies to additional T cell surface determinants

The effect of soluble or immobilized MAb directed at various additional surface proteins on the proliferation of highly puri-fied T4 cells induced by two immobilized MAb to CD3, OKT3 and 64.1, was examined. High density 64.1 stimulated nearly all T4 cells to enter and progress through the cell cycle. Maxi-mal T4 cell proliferation required stimulation with immobilized 64.1 throughout the length of the incubation and was not ef-fected by any of the additional soluble or immobilized MAb employed. In contrast, low density immobilized 64.1 and all densities of immobilized OKT3 employed stimulated a minor-ity of the cells to enter the cell cycle and proliferate. Immobi-lized MAb directed at CD2, class I major histocompatibility complex (MHC) encoded gene products or CD11a (LFA-1) dramatically enhanced the response, whereas soluble MAb di-rected at these determinants did not. Both immobilized and soluble MAb directed at CD5 and CD28 (Tp44) enhanced re-sponses, but they were less effective than immobilized MAb to CD2, LFA-1 or HLA-A,B,C. Soluble anti-CD4 MAb inhibited responses somewhat, whereas immobilized anti-CD4 enhanced responses. Costimulation was observed when MAb to CD3 and class I MHC molecules but not CD2, LFA-1 or CD4 were immobilized to separate surfaces. The data suggest that when anti-CD3 stimulation is suboptimal, responses can be en-hanced by MAb to CD5 or CD28 (Tp44) or by immobilized MAb to CD4, CD2, CD1la (LFA-1), or class I MHC encoded gene products. Although crosslinking of CD4, CD2, or CDlla with CD3 may be necessary for costimulation, immobilized MAb to CD3 and class I MHC molecules appear to deliver independent signals that result in enhanced T4 cell activation and proliferation