Involvement of NKR-P2/NKG2D in DC-mediated killing of tumor targets: indicative of a common, innate, target-recognition paradigm?

Abstract

DC are the most efficient antigen-presenting cells that regulate the immune response. Here, we demonstrate the expression of NK cell receptor protein-2 (NKR-P2) on rat and mouse DC, and we show that NKR-P2 gets reorganized upon antigen contact. DC activated with anti-NKR-P2 mAb exhibit enhanced apoptotic killing of tumor targets, whereas blocking the interaction between NKR-P2 and its ligand with rNKR-P2 abrogated apoptotic killing, suggesting NKR-P2 to function as an activating molecule on DC. In vivo injection of anti-NKR-P2 mAb augmented DC activity and delayed tumor progression. NKR-P2 signaling involved Ca(2+ )influx, culminating in the expression of the apoptosis-inducing molecule, TNF-alpha. Taken together, these observations suggest that NKR-P2 (the rat orthologue of human NKG2D) acts as a target-recognition molecule on DC.

• Authors: Rajshekhar Alli, Balasubramanian Savithri, Suvendu Das, Chavvakula Varalakshmi, Nandini Rangaraj, Ashok Khar
• Journal: European journal of immunology (Eur J Immunol) Vol. 34 Issue 4 Pg. 1119-26 (Apr 2004) ISSN: 0014-2980 [Print] Germany
• PMID: 15048723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lectins, C-Type
• NK Cell Lectin-Like Receptor Subfamily K
• NKR-P2 protein, rat
• Receptors, Immunologic
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Antigen Presentation (immunology)
• Apoptosis (immunology)
• Cytotoxicity Tests, Immunologic
• Cytotoxicity, Immunologic
• Dendritic Cells (immunology)
• Flow Cytometry
• Fluorescent Antibody Technique
• Lectins, C-Type (immunology)
• Lymphocyte Activation (immunology)
• Male
• Mice
• Microscopy, Confocal
• NK Cell Lectin-Like Receptor Subfamily K
• Neoplasms, Experimental (immunology)
• Rats
• Receptors, Immunologic (immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (analysis, immunology)