CD300c is uniquely expressed on CD56bright Natural Killer Cells and differs from CD300a upon ligand recognition

Authors

• M Dimitrova
• O Zenarruzabeitia
• FR Borrego
• VR Simhadri

Abstract

Paired receptors on NK cells have the ability to recognize similar ligands with varied strength of binding ability and perform different functions. These paired receptors, called CD300 molecules, are emerging as novel immune regulators in health and disease due to their interaction with their lipid-nature ligands. Particularly, the paired receptors CD300c and CD300a have been shown to elicit activating and inhibitory capabilities respectively. In the current study, we seek to investigate the expression and function of CD300c on human NK cells. We demonstrate that expression of CD300c is uniquely induced on CD56bright NK cells upon treatment with either IL-2 or IL-15. In addition, we show that this expression is inhibited in the presence of IL-4 and is regulated by the transcription factor STAT-5. Moreover, we specifically demonstrate that IL-2 secreted from activated CD4+ T cells is responsible for the expression of CD300c on CD56bright NK cells. Activation with a specific monoclonal antibody targeting CD300c enhances the proficiency of CD56bright NK cells to degranulate and induce chemokine and cytokine secretion. Also, we demonstrate the differential binding of CD300a and CD300c to their ligands phosphatidylethanolamine (PE) and phosphatidylserine (PS) and their differential ability to affect CD56bright NK cell functions. Our results provide an insight into a novel set of paired receptors CD300a and CD300c that are distinctively expressed on CD56bright NK cells with varied effector functions.

Scientific Focus Area: Immunology

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