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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2858-2866.
Prepublished online as a Blood First Edition Paper on July 6, 2004; DOI 10.1182/blood-2004-03-0878.
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Submitted March 8, 2004
Accepted June 29, 2004
KLRL1, a novel killer cell lectin-like receptor, inhibits natural killer cell cytotoxicity
Yanmei Han, Minghui Zhang, Nan Li, Taoyong Chen, Yi Zhang, Tao Wan, and Xuetao Cao*
Institute of Immunology, Second Military Medical University, Shanghai, China
* Corresponding author; email: caoxt{at}public3.sta.net.cn.
NK cell inhibitory receptors play important roles in the regulation of target susceptibility to natural killing. Here we report the molecular cloning and functional characterization of a novel NK cell receptor, KLRL1, from human and mouse dendritic cells. KLRL1 is a type II transmembrane protein with an immunoreceptor tyrosine-based inhibitory motif and a C-type lectin-like domain. The KLRL1 gene is located in the central region of the NK gene complex in both humans and mice, on human chromosome 12p13 and mouse chromosome 6F3, adjacent to the other KLR genes. KLRL1 is preferentially expressed in lymphoid tissues and immune cells including NK cells, T cells, dendritic cells and monocytes/macrophages. Western blot and fluorescence confocal microscopy analyses indicated that KLRL1 is a membrane-associated glycoprotein, which forms a heterodimer with an as yet unidentified partner. Human and mouse KLRL1 are both predicted to contain putative immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoprecipitation experiments demonstrated that KLRL1 associates with the tyrosine phosphatases SHP-1 and SHP-2. Consistent with its potential inhibitory function, pretreatment of target cells with human KLRL1-Fc fusion protein enhances NK-mediated cytotoxicity. Taken together, our results demonstrate that KLRL1 belongs to the KLR family and is a novel inhibitory NK cell receptor.

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