Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells

• Published in: Nature immunology Vol. 10; no. 9; pp. 973 - 980
• Main Authors: Dong, Zhongjun, Veillette, André, Zhong, Ming-Chao, Chen, Riyan, Latour, Sylvain, Cruz-Munoz, Mario-Ernesto
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2009; Nature Publishing Group
• Subjects: Adaptor Proteins, Signal Transducing - physiology; Animals; Antigens, CD - physiology; Antigens, Ly - physiology; Biomedical and Life Sciences; Biomedicine; CD48 Antigen; CHO Cells; Cricetinae; Cricetulus; Hematopoietic stem cells; Hematopoietic System - cytology; Histocompatibility Antigens Class I - physiology; Immune system; Immunology; Infectious Diseases; Interferon-gamma - biosynthesis; Intracellular Signaling Peptides and Proteins - physiology; Killer cells; Killer Cells, Natural - physiology; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; NK Cell Lectin-Like Receptor Subfamily K - physiology; Physiological aspects; Rats; Signaling Lymphocytic Activation Molecule Associated Protein; Signaling Lymphocytic Activation Molecule Family; Transcription Factors - physiology
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.1763

SAP family adaptors, including SAP, EAT-2 and ERT, individually influence natural killer cell function. Veillette and colleagues show that natural killer cells lacking all three adaptors fail to eliminate unwanted hematopoietic cells. The adaptors SAP, EAT-2 and ERT are specific to cells of the immune system and belong to the SAP family. All three are expressed in natural killer (NK) cells. Here we examined the global function of the SAP family using mice lacking SAP, EAT-2 and ERT. These adaptors acted together in a mechanism that was essential for the elimination of hematopoietic but not nonhematopoietic cells by NK cells. This function was mediated by many receptors of the SLAM family on NK cells that were engaged by ligands found solely on hematopoietic cells. In the absence of SAP-related adaptors, SLAM receptors lost their activating function and became inhibitory receptors that repressed other activating receptors, such as NKG2D. Hence, the SAP family is essential for the elimination of unwanted hematopoietic cells by NK cells.