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Surface molecules involved in CD3-negative NK cell function. A novel molecule which regulates the activation of a
A Moretta1, E Ciccone, G Tambussi
1Istituto Nazionale per la Ricerca sul Cancro, Genoa; Italy.
Abstract:
Natural killer cells are characterized by the lack of CD3/TCR molecules and by the expression of CD16 and CD56 (NKHI or Leu19) surface antigens. In addition to their ability to lyse certain tumor target cells, they release lymphokines including tumor necrosis factor and interferon gamma. Another unexpected functional capability of at least some NK cells is the ability to specifically recognize and lyse certain normal allogeneic cells (PHA-induced blasts). MAbs directed to CD2 or to CD16 surface molecules induced triggering of NK cells leading to target cell (p815) lysis in a redirected killing assay. Importantly, different from induction of T cell activation, single anti-CD2 MAbs were sufficient to trigger NK cell function. Another MAb (GL183) inducing NK cell triggering recognized a novel surface molecules expressed on 20-50% of resting or cultured NK cells. Cloned GL183+ cells displayed a variable degree of cytolytic activity against a number of human target cells of different histotype; moreover, this activity was strongly enhanced by the addition of GL183 MAb. On the other hand, GL183 MAb inhibited lysis of murine lines (including P815). Thus on P815 target cells GL183 MAb has an effect antithetical to that of other stimuli including PHA, anti-CD2 or anti-CD16 MAbs. GL183 MAb, added simultaneously to one or another of the stimuli above, strongly inhibited the target cell lysis induced by these stimuli. Thus, GL183 may represent an important molecule in the process of activation/regulation of phenotypically-defined NK cell subsets.
Insights
Natural killer (NK) cells, identified by CD16 and CD56 antigens, can lyse tumor cells and normal blasts. A novel molecule, GL183, regulates NK cell activity, inhibiting lysis in some contexts while enhancing it in others.
Area of Science:
- Immunology
- Cell Biology
Background:
- Natural killer (NK) cells are lymphocytes crucial for innate immunity, characterized by CD16 and CD56 surface antigens and lacking CD3/TCR molecules.
- NK cells possess cytotoxic functions against tumor cells and can also lyse certain allogeneic cells, such as PHA-induced blasts.
- NK cell activation can be triggered by monoclonal antibodies (MAbs) targeting surface molecules like CD2 and CD16.
Purpose of the Study:
- To investigate the functional role of a novel surface molecule recognized by the GL183 MAb in NK cell activation and regulation.
- To characterize the impact of GL183 MAb on NK cell-mediated cytotoxicity against various target cells.
Main Methods:
- Utilized monoclonal antibodies (MAbs) against CD2, CD16, and the novel GL183 surface molecule to trigger NK cell function.
- Performed redirected killing assays using target cells like P815 to assess NK cell cytotoxicity.
- Analyzed the effect of GL183 MAb, alone and in combination with other stimuli, on NK cell-mediated lysis of murine and human target cells.
Main Results:
- Single anti-CD2 MAbs were sufficient to trigger NK cell function, distinct from T cell activation.
- The GL183 MAb recognized a novel surface molecule present on a subset of NK cells (20-50%).
- Cloned GL183+ NK cells showed enhanced cytolytic activity against human target cells when treated with GL183 MAb, but GL183 inhibited lysis of murine P815 cells, acting antagonistically to other stimuli.
Conclusions:
- GL183 MAb plays a regulatory role in NK cell activation, with context-dependent effects on cytotoxicity.
- The novel GL183 molecule may be important for regulating phenotypically defined NK cell subsets.
- GL183 represents a potential target for modulating NK cell-mediated immune responses.