The CD2 T lymphocyte-surface glycoprotein serves to mediate adhesion between T lymphocytes and their cognate cellular partners which express the specific ligand LFA-3. In addition, CD2 by itself or in conjunction with T-cell receptor stimulation, transduces signals resulting in T-lymphocyte activation. One or both of these functions seems to be physiologically important, given that certain anti-CD2 monoclonal antibodies block T-cell activation and that antigen-responsive memory T cells express a high level of CD2 relative to virgin T cells, which are largely antigen-unresponsive. Nevertheless, the contribution of the individual CD2 functions in T-cell responses has not been independently examined. To this end, human CD2 complementary DNAs encoding an intact LFA-3-binding adhesion domain, but lacking a functional cytoplasmic signal transduction element (CD2trans-), were introduced into an ovalbumin-specific, I-Ad restricted murine T-cell hybridoma. The antigen-specific response of T hybridoma cells expressing human CD2trans- protein was enhanced up to 400% when the human LFA-3 ligand was introduced into the I-Ad expressing murine antigen-presenting cells. In contrast, no augmentation was observed if human LFA-3 was absent or expressed on a third-party cell lacking the I-Ad restriction element. These results directly demonstrate the functional significance of adhesion events mediated between CD2 on the antigen-responsive T lymphocyte and LFA-3 on the presenting cell in optimizing antigen-specific T-cell activation.