Education/Licensing Imparts Differences in the Adhesive Interaction of NK Cells with Target Cells

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIAID	IMMUNO-21

Authors

• L. M. Thomas
• E. O. Long

Abstract

Natural killer (NK) cells act in cytotoxic lymphocyte-mediated killing of target cells, such as tumor cells or pathogen-infected cells. Activating and stochastically expressed inhibitory receptors modulate several critical events for efficient NK-mediated killing of target cells, including conjugation of NK cell to target cells, polarization of NK cell lytic granules towards target cells, and lytic granule degranulation. NK cell education (aka licensing) is a process that renders inhibitory receptor deficient NK cells to be inherently less responsive to activating stimuli than NK cells that express inhibitory receptors. Through my research, I have observed that uneducated NK cells not only exhibit decreased levels of cytotoxicity, but also display decreased conjugation to target cells than educated NK cells (i.e., NK cells that possess inhibitory receptors) in part due to altered LFA-1 receptor and ICAM-1 ligand interactions. Surprisingly, I have also observed that uneducated NK cells specifically polarize their lytic granules towards target cells as efficiently as educated NK cells despite the fact that lytic granule polarization is mediated through LFA-1 and ICAM-1 interactions. These results demonstrate potentially different signaling capabilities downstream of LFA-1 between educated and uneducated NK cells.

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