Anti-L3T4 antibody inhibits the lysis of H-2 class II antigen-negative target cells by L3T4+ cytotoxic T lymphocytes.

Anti-L3T4 monoclonal antibodies inhibit the cytotoxic activity of L3T4+ cytotoxic T lymphocytes specific for H-2 class I antigens. The P815 target cells used to detect this population of murine cytolytic cells are shown by immunofluorescence, radioimmunoprecipitation, and RNA blot analysis not to express H-2 class II protein or mRNA. Contrary to previously proposed models regarding its function, we conclude that the L3T4 molecule is involved at some stage of the lytic interaction between the class I-specific L3T4+ effector cell and its target cell by a mechanism for which there is not an obligatory requirement for H-2 class II antigen expression by the target cell. L3T4 may be an early component of the system that transduces the activation signal from the T-cell receptor complex to the cytoplasm, a cell-surface receptor for a yet undefined natural ligand that delivers a negative signal to the killer T cell, or it may modulate the avidity of the antigen-specific T-cell receptor through a direct physical association with it.