T lymphocyte-mediated cytolysis. III. Delineation of mechanisms whereby mitogenic and non-mitogenic lectins mediate lymphocyte-target interaction.

We have investigated the mechanism(s) by which mitogenic (concanavalin A [Con A], phytohaemagglutinin [PHA] and Lens culinaris agglutinin [LCA]) and non-mitogenic (soybean agglutinin, peanut agglutinin, wheat-germ agglutinin and pokeweed mitogen) lectins mediate, non-specifically, lectin-dependent lymphocytotoxicity (LDCC). We show that non-mitogenic lectins are ineffective mediators of LDCC, due to their inability to mediate effective binding of effector cytotoxic T cells (EC) and target cells (TC), and not to their failure to 'activate' TC-bound EC, as proposed before. Evidence is presented that in LDCC Con A and PHA exert their primary effect(s) by affecting the TC rather than the EC. Although the lectin LCA, unlike Con A and PHA, is equally reactive with either EC or TC, a direct comparison is difficult since the presence of LCA, but not Con A or PHA, during the entire assay is required for optimal kill. Furthermore, all three LDCC-supportive lectins (PHA, Con A and LCA) show a similar TC preference when tested in a EC-TC conjugation assay. Taken together, these results are inconsistent with the theory that lectins mediate LDCC by 'bridging' EC and TC through lectin-binding receptors followed by 'activation' of the TC-bound EC. We would like to suggest that the potential of mitogenic lectins to mediate EC-TC interaction is related to their modification of TC-surface constituents, possibly major histocompatibility complex determinants, rendering them recognizable, non-specifically by EC.