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Kyoko Tajima, Naoki Matsumoto, Kazuji Ohmori, Haruka Wada, Masayuki Ito, Kazuhiro Suzuki, Kazuo Yamamoto, Augmentation of NK cell‐mediated cytotoxicity to tumor cells by inhibitory NK cell receptor blockers, International Immunology, Volume 16, Issue 3, March 2004, Pages 385–393, https://doi.org/10.1093/intimm/dxh021
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Abstract
NK cells monitor expression of MHC class I by inhibitory receptors and preferentially kill cells that lose or down‐regulate MHC class I expression. One possible mechanism by which tumor cells evade NK cell killing is continued expression of appropriate MHC class I ligands to engage inhibitory receptors on NK cells. We show here that small‐mol.‐wt blockers against the mouse inhibitory NK cell receptor Ly49A enhance NK cell killing of such tumor cells. We identified Ly49A‐binding peptides by selecting phages with the capacity to bind recombinant Ly49A expressed in Escherichia coli from a phage display random peptide library. The Ly49A‐binding peptides could also bind Ly49A expressed on mammalian cells. Importantly, the Ly49A‐binding peptides blocked Ly49A recognition of its MHC class I ligands H‐2Dd and H‐2Dk. Moreover, blockade of Ly49A by the peptides enhanced cytotoxicity of Ly49A+ NK cells towards H‐2Dd‐expressing tumor cells. These results clearly indicate effectiveness of small‐mol.‐wt blockers of inhibitory NK cell receptors in enhancing NK cell‐mediated killing of tumor cells that are otherwise resistant because of MHC class I expression.
