Involvement of NKR-P2/NKG2D in DC-mediated killing of tumor targets: indicative of a common, innate, target-recognition paradigm?
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.
Alli
Rajshekhar
R
Centre for Cellular and Molecular Biology, Hyderabad, India.
Savithri
Balasubramanian
B
Das
Suvendu
S
Varalakshmi
Chavvakula
C
Rangaraj
Nandini
N
Khar
Ashok
A
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D037181:Lectins, C-Type / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009374:Neoplasms, Experimental / Q000276:immunology; D051381:Rats; D011971:Receptors, Immunologic / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
D037181:Lectins, C-Type; D055655:NK Cell Lectin-Like Receptor Subfamily K; C113208:NKR-P2 protein, rat; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha