This study was designed to define regions on the human CD4 molecule important for the class II-dependent activation of resting, polyclonal CD4 T cells. With the use of mAb to known epitopes on CD4, we assayed the degree of CD4 saturation and functional effects on T cell activation over a range of antibody concentrations in parallel titration experiments. This approach allows a quantitative comparison of different reagents, regardless of parameters such as affinity for CD4. In sharp contrast to results reported for preactivated T cells and CD4 transfected T cell hybridomas, all 22 CD4 mAb tested did inhibit proliferative responses of freshly isolated CD4 T cells to MHC class II Ag. At the lowest saturating concentration of each antibody, T cell proliferation was reduced by 45 to 82%. Inhibition did not depend on antibody-induced modulation of CD4 expression. Strikingly, no correlation was found between the functional effects and the specificity of the mAb for different epitopes on CD4, such as the putative binding sites for MHC class II or HIV glycoprotein gp120.

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