HLA class I1 molecules on monocytes regulate T cell proliferation through physical interaction in the CD3 activation pathway*
HLA class I1 molecules are involved in the OKT3-induced Tcell activation, since monoclonal antibodies (mAb) to monomorphic determinants of class I1 antigens are able to inhibit Tcell proliferation. This effect involves several of the events leading toTcell activation and proliferation, i.e. interleukin (IL) 1, IL6 and IL2 secretion and IL2 receptor expression. The main target of the inhibition is represented by monocytes, and the interference of anti-class I1 mAb in the direct interaction of monocytes with T cells is likely to play a relevant role in the inhibition mechanism.To test this hypothesis,we investigated in the present study the effect of anti-class I1 mAb on the proliferation of Tcells stimulated with mAb OKT3 in the presence of paraformaldehyde-treated monocytes. We show that the inhibition of proliferation is specific and dose dependent, and seems to involve particular class I1 epitopes. Addition of fixed monocytes to inhibited T cell cultures restores proliferation to a moderate extent, only if monocytes are added within the first 12 h of culture, suggesting that class I1 antigens or spatially related molecules deliver signals concurrently with the mitogenic stimulus. The blocking capability of anti-class I1 mAb was not restricted to the CD4+ or the CD8+ Tcell subsets, suggesting that, under inhibitory conditions, these mAb affect other structures on the T cell surface, relevant to the monocyte-T cell interaction.