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The Journal of Immunology, Vol 139, Issue 6 1772-1779, Copyright © 1987 by American Association of Immunologists

ARTICLES

Induction of calcium flux and enhancement of cytolytic activity in natural killer cells by cross-linking of the sheep erythrocyte binding protein (CD2) and the Fc-receptor (CD16)

C Anasetti, PJ Martin, CH June, KE Hellstrom, JA Ledbetter, PS Rabinovitch, Y Morishita, I Hellstrom and JA Hansen

Binding of the anti-cluster of differentiation (CD) 2 monoclonal antibody 9-1 causes an increase in the concentration of cytoplasmic- free calcium ([Ca2+]i) in cultured CD3-/CD16+ natural killer (NK) cells. This response did not occur in cultured CD3+/CD16- cytotoxic T lymphocytes (CTL). Anti-CD16 antibodies could partially block the calcium response when NK cells were stimulated with intact antibody 9- 1, and antigen-binding fragment F(ab')2 of antibody 9-1 did not produce a calcium response. Thus an interaction of the 9-1 antibody with CD16 Fc receptors was required for the functional effect. The dual interaction of antibody 9-1 with both CD2 and CD16 was demonstrated by comodulation experiments. The cytolytic activity of cultured NK cells was increased by antibody 9-1 but not by F(ab')2 fragments of antibody 9-1. The enhanced lytic activity was blocked by anti-CD16 antibody, anti-CD18 antibody, and anti-CD2 antibodies that do not block the binding of antibody 9-1. This pattern was distinct from antibody- dependent cell-mediated cytotoxicity which was blocked only by the anti- CD16 antibody. Thus antibody 9-1 enhanced cytotoxicity by activating effector cells. There was no enhancement of lytic activity when F(ab')2 of antibody 9-1 were cross-linked with a polyclonal antiglobulin, even though [Ca2+]i was increased. These results show that induction of a [Ca2+]i response is not sufficient to enhance lytic activity in NK cells, and suggest that signals delivered through CD16 are necessary.


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R Giorda, W. Rudert, C Vavassori, W. Chambers, J. Hiserodt, and M Trucco
NKR-P1, a signal transduction molecule on natural killer cells
Science, September 14, 1990; 249(4974): 1298 - 1300.
[Abstract] [PDF]


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