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CEACAM 1 on activated NK cells inhibits NKG 2 D ‐mediated cytolytic function and signaling
Author(s) -
Hosomi Shuhei,
Chen Zhangguo,
Baker Kristi,
Chen Lanfen,
Huang YuHwa,
Olszak Torsten,
Zeissig Sebastian,
Wang Jing H.,
Mandelboim Ofer,
Beauchemin Nicole,
Lanier Lewis L.,
Blumberg Richard S.
Publication year - 2013
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201242676
Subject(s) - nkg2d , cytolysis , biology , microbiology and biotechnology , receptor , in vitro , cytotoxicity , biochemistry
Carcinoembryonic antigen‐related cell adhesion molecule 1 ( CEACAM 1) is expressed on activated natural killer ( NK ) cells wherein it inhibits lysis of CEACAM 1‐bearing tumor cell lines. The mechanism for this is unknown. Here, we show that interleukin‐2‐induced expression of CEACAM 1 on both mouse and primary human NK cells impairs the ability of NK gene complex group 2 member D ( NKG 2 D ) to stimulate cytolysis of CEACAM 1‐bearing cells. This process requires the expression of CEACAM 1 on the NK cells and on the tumor cells, which is consistent with the involvement of trans‐homophilic interactions between CEACAM 1. Mechanistically, co‐engagement of NKG 2 D and CEACAM 1 results in a biochemical association between these two surface receptors and the recruitment of Src homology phosphatase 1 by CEACAM 1 that leads to dephosphorylation of the guanine nucleotide exchange factor V av1 and blockade of downstream signaling that is associated with the initiation of cytolysis. Thus, CEACAM 1 on activated NK cells functions as an inhibitory receptor for NKG 2 D ‐mediated cytolysis, which has important implications for understanding the means by which CEACAM 1 expression adversely affects tumor immunity.