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HLA‐B‐Associated Transcript 3 (BAT3), a ligand for Nkp30 is secreted from cells as Exosomes and enhances the activity of Natural Killer cells
Author(s) -
Simhadri Venkateswara Rao,
Reiners Katrin S,
Hansen Hinrich P,
Engert Andreas,
Strandmann Elke Pogge
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1076.9
Subject(s) - biology , microvesicles , microbiology and biotechnology , innate immune system , immune system , acquired immune system , microvesicle , immunology , microrna , biochemistry , gene
Natural Killer (NK) cells, defined as innate lymphocytes also serve as regulators of adaptive immunity via cytokine secretion and cross‐talk with dendritic cells (DCs). Both killing and maturation of DCs by NK cells is dependent on NKp30, a Natural Cytotoxicity Receptor (NCR) expressed on NK cells. However, the NKp30 specific cellular ligands have remained elusive. Recently BAT3 was identified as the tumor associated ligand for NKp30 (Immunity, 2007 in press). It is a nuclear protein characterized by a conserved BAG domain (BclBcl‐2 associated anthogene), that interacts with Hsp70. This abstract describes that BAT3 is secreted into the extracellular environment in exosomal fractions upon exposure to stress signals. The exosomes from the tumor cells and iDCs possess BAT3 on the surface. These exosomes activate NK cells and stimulate the cytokine release TNFalpha and IFNgamma. This release was enhanced by exosomes from cells overexpressing BAT3 and was inhibited by depleting the overexpressed BAT3. Moreover, the exosomes’ stimulation was inhibited when the cells were targeted with siRNA of BAT3. Thus we postulate that BAT3, a novel cellular ligand for NKp30 receptor has a role in the reciprocal activation of NK‐DC cross‐talk. We present evidence that BAT3 is secreted into exosomes, a novel group of immune regulators “Nucleokines”. Research was supported by Deutsche Forschungsgemeinschaft (DFG) (STR 530/5‐1).