In this study, we utilized two anti-T11 monoclonal antibodies (mAbs) that inhibited the specific cytolytic activity of mixed lymphocyte culture (MLC) activated T cells to analyze, at the clonal level, the involvement of T11 molecules in 1) antigen specific versus non-specific mechanisms of target cell lysis 2) antigen-driven T cell proliferation and IL-2 production versus IL-2-induced cell proliferation. In contrast to anti-T3 or anti-T8 mAbs, antibodies to T11 molecules inhibited the cytolytic activity of MLC-derived allospecific clones in a uniform manner. In addition, anti-T11 antibodies inhibited the specific activity of CTL clones resistant to anti-T3 antibodies, even after antibody-induced modulation of T3 molecules (while anti-T3 mAbs had no effect). Similarly, anti-T11 antibodies inhibited the alloantigen induced proliferation and IL-2 release of alloreactive clones independent on their T4+ or T8+ phenotype. The inhibitory activity of anti-T11 antibodies appears to be confined to antigen-specific T cell functions since neither natural killer-like activity of CTL clones nor the IL-2 induced clonal proliferation was affected. Thus, our results indicate that T11 molecules are functionally involved in antigen recognition by T cell regardless of their function and T4/T8 phenotype.