Abstract
Activation of natural killer cells can be mediated by different receptors. Stimulation of the receptors 2B4, NTB-A and CRACC, members of the SLAM-related receptor family, induces cytotoxicity and cytokine production. The surface expression of 2B4 and other activating natural killer cell receptors is down-modulated after receptor engagement, which results in a weaker response to consecutive stimulation. We tested whether this regulatory mechanism applies to all SLAM-related receptors expressed by primary human natural killer cells. After co-culture with target cells expressing the respective ligands different effects on receptor surface expression were observed. While 2B4 ex-pression was strongly reduced, NTB-A showed less prominent down-modulation and the expression level of CRACC remained unchanged. The expression levels of the receptor-proximal signaling molecules SAP, EAT-2 and FynT did not change after receptor engagement. Co-culture with target cells expressing the ligands for NTB-A or CRACC had no impact on subsequent NTB-A or CRACC-mediated NK cell activation.
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