activation of nk cells by an endocytosed receptor for soluble hla-g激活nk细胞的内源性可溶性hla-g受体.pdfVIP

PLoS BIOLOGY Activation of NK Cells by an Endocytosed Receptor for Soluble HLA-G 1 1 1 2 3 Sumati Rajagopalan , Yenan T. Bryceson , Shanmuga P. Kuppusamy , Daniel E. Geraghty , Arnold van der Meer , 3 1* Irma Joosten , Eric O. Long 1 Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America, 2 Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 3 Department of Blood Transfusion and Transplantation Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands Signaling from endosomes is emerging as a mechanism by which selected receptors provide sustained signals distinct from those generated at the plasma membrane. The activity of natural killer (NK) cells, which are important effectors of innate immunity and regulators of adaptive immunity, is controlled primarily by receptors that are at the cell surface. Here we show that cytokine secretion by resting human NK cells is induced by soluble, but not solid-phase, antibodies to the killer cell immunoglobulin-like receptor (KIR) 2DL4, a receptor for human leukocyte antigen (HLA)-G. KIR2DL4 was constitutively internalized into Rab5-positive compartments via a dynamin-dependent process. Soluble HLA-G was endocytosed into KIR2DL4–containing compartments in NK cells and in 293T cells transfected with KIR2DL4. Chemokine secretion induced by KIR2DL4 transfection into 293T cells occurred only with recombinant forms of KIR2DL4 that t