MHC class I-independent recognition of NK-activating receptor KIR2DS4.

Abstract

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 KIRs) 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.

• Authors: Gil Katz, Roi Gazit, Tal I Arnon, Tsufit Gonen-Gross, Gabi Tarcic, Gal Markel, Raizy Gruda, Hagit Achdout, Olga Drize, Sharon Merims, Ofer Mandelboim
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 173 Issue 3 Pg. 1819-25 (Aug 01 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15265913 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-C Antigens
• HLA-C*04 antigen
• Histocompatibility Antigens Class I
• Immunoglobulin Fc Fragments
• Immunoglobulin G
• KIR2DS4 protein, human
• Ligands
• Neoplasm Proteins
• Receptors, Immunologic
• Receptors, KIR
• Recombinant Fusion Proteins

Topics

• Amino Acid Sequence
• Animals
• Binding Sites
• COS Cells
• Cell Line, Tumor (immunology)
• Chlorocebus aethiops
• Cytotoxicity, Immunologic
• HLA-C Antigens (immunology)
• Histocompatibility Antigens Class I (immunology)
• Humans
• Immunoglobulin Fc Fragments (genetics)
• Immunoglobulin G (genetics)
• Killer Cells, Natural (immunology)
• Ligands
• Melanoma (chemistry, immunology, pathology)
• Models, Molecular
• Molecular Sequence Data
• Mutagenesis, Site-Directed
• Neoplasm Proteins (immunology, isolation & purification, metabolism)
• Protein Binding
• Protein Conformation
• Receptors, Immunologic (chemistry, immunology, metabolism)
• Receptors, KIR
• Recombinant Fusion Proteins (immunology)
• Sequence Alignment
• Sequence Homology, Amino Acid
• Transfection