The majority of human CD3 epitopes are conferred by the epsilon chain

Transgenic mouse T cells expressing the human CD3ε chain bind the majority (29/36) of monoclonal antibodies (mAbs) specific for human CD3. A proportion of these mAbs are also able to recognize isolated CD3ε in a soluble, recombinant form. Thus, CD3ε can confer most CD3 epitopes on the TCR-CD3 complex, but many determinants may require assembly of the complex for their formation. A number ot mAbs did not recognize ε-transgenic T cells and probably need other CD3 subunits for binding. CD3-specific mAbs from each of the three groups defined here, as well as mAbs directed against the TCRαβ heterodimer, are all able to activate T cells. Therefore mAb attachment at several different sites on the TCR-CD3 complex can give rise to activation signals. This suggests that the cross-linking function of mitogenic antibodies may be their most significant property, rather than the perturbation of a particular 'functional epitope'.