The CD56 differentiation antigen, recognized by anti-Leu-19 and NKH-1 mAbs, is a 200-220-kD glycoprotein that is expressed predominantly on human NK cells and a minor subset of T lymphocytes mediating MHC-unrestricted cytotoxicity. The recent finding that CD56 is an isoform of the neural cell adhesion molecule (N-CAM) prompted us to examine the adhesive function of CD56 in the NK-target cell interaction. Synergistic inhibitory effects of anti-CD56 mAbs with anti-LFA-1 and/or anti-LFA-3 mAbs were demonstrated on NK cell-mediated cytotoxicity and on NK cell binding to target cells only when the target cells also express CD56. These findings indicate that CD56 on NK cells can serve as the third pathway of cell adhesion other than those mediated by the CD2/LFA-3 and LFA-1/ICAM-1 interactions, and is involved in NK cell cytotoxicity when interacting with the cells bearing N-CAM.

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