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Granule polarization is the preferred target for inhibition by NK cell inhibitory receptors.
Author(s) -
Das Asmita,
Long Eric
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1064.1
Subject(s) - degranulation , microbiology and biotechnology , cd16 , receptor , mhc class i , transfection , biology , chemistry , major histocompatibility complex , immunology , cell culture , immune system , biochemistry , cd8 , genetics , cd3
NK cells kill target cells by polarized release of cytotoxic granules. Granule polarization and degranulation are controlled by different signals in NK cells. The integrin LFA‐1 signals for polarization but not degranulation, whereas the Fc receptor CD16 induces degranulation but not polarization. Lysis of target cells by NK cells is controlled by inhibitory receptors specific for MHC class I. To test the sensitivity to inhibition of polarization and degranulation separately, NK cells were mixed with insect cells expressing ICAM‐1 (ligand of LFA‐1) and MHC class I in the presence or absence of rabbit IgG (ligand of CD16) bound to the insect cells. Engagement of inhibitory receptors by their MHC ligands completely blocked polarization but not degranulation. Similar results were obtained during natural cytotoxicity (independent of CD16) against human K562 cells transfected with MHC class I. Thus, either degranulation is not sensitive to inhibitory signals or inhibition of degranulation requires additional receptor – ligand interactions. Inhibition of degranulation occurred with the human target cell 221 transfected with MHC class I. These data demonstrate that (1) granule polarization is a preferred target of inhibitory signals, and (2) as yet unknown receptor – ligand interactions contribute to inhibition of degranulation.