TY - JOUR
T1 - MHC class I-independent recognition of NK-activating receptor KIR2DS4
AU - Katz, Gil
AU - Gazit, Roi
AU - Arnon, Tal I.
AU - Gonen-Gross, Tsufit
AU - Tarcic, Gabi
AU - Markel, Gal
AU - Gruda, Raizy
AU - Achdout, Hagit
AU - Drize, Olga
AU - Merims, Sharon
AU - Mandelboim, Ofer
PY - 2004/8/1
Y1 - 2004/8/1
N2 - Natural killer cells are capable of killing tumor and virus-infected cells. This killing is mediated primarily via the natural cytotoxicity receptors, including NKp46, NKp44, NKp30, and by the NKG2D receptor. Killer cell Ig-like receptors (KIRs) are mainly involved in inhibiting NK killing (inhibitory ICIRs) via interaction with MHC class I molecules. Some KIRs, however, have been found to enhance NK killing when interacting with MHC class I molecules (activating KIRs). We have previously demonstrated that KIR2DS4, an activating KIR, recognizes the HLA-Cw4 protein. The interaction observed was weak and highly restricted to HLA-Cw4 only. These findings prompted us to check whether KIR2DS4 might have additional ligand(s). In this study, we show that KIR2DS4 is able to also interact with a non-class I MHC protein expressed on melanoma cell lines and on a primary melanoma. This interaction is shown to be both specific and functional. Importantly, site-directed mutagenesis analysis reveals that the amino acid residues involved in the recognition of this novel ligand are different from those interacting with HLA-Cw4. These results may shed new light on the function of activating KIRs and their relevance in NK biology.
AB - Natural killer cells are capable of killing tumor and virus-infected cells. This killing is mediated primarily via the natural cytotoxicity receptors, including NKp46, NKp44, NKp30, and by the NKG2D receptor. Killer cell Ig-like receptors (KIRs) are mainly involved in inhibiting NK killing (inhibitory ICIRs) via interaction with MHC class I molecules. Some KIRs, however, have been found to enhance NK killing when interacting with MHC class I molecules (activating KIRs). We have previously demonstrated that KIR2DS4, an activating KIR, recognizes the HLA-Cw4 protein. The interaction observed was weak and highly restricted to HLA-Cw4 only. These findings prompted us to check whether KIR2DS4 might have additional ligand(s). In this study, we show that KIR2DS4 is able to also interact with a non-class I MHC protein expressed on melanoma cell lines and on a primary melanoma. This interaction is shown to be both specific and functional. Importantly, site-directed mutagenesis analysis reveals that the amino acid residues involved in the recognition of this novel ligand are different from those interacting with HLA-Cw4. These results may shed new light on the function of activating KIRs and their relevance in NK biology.
UR - http://www.scopus.com/inward/record.url?scp=3242766673&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.173.3.1819
DO - 10.4049/jimmunol.173.3.1819
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C2 - 15265913
AN - SCOPUS:3242766673
SN - 0022-1767
VL - 173
SP - 1819
EP - 1825
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -