Activation of NK Cells by an Endocytosed Receptor for Soluble HLA-G

• DOI: 10.1371/journal.pbio.0040009
• Publication Date: 2005-12-20T17:20:14Z
• Authors: Sumati Rajagopalan; Yenan T Bryceson; Shanmuga P Kuppusamy; Daniel E Geraghty; Arnold van der Meer; Irma Joosten; Eric O Long
• Keywords: Dynamins; 0301 basic medicine; NCMLS 2: Immune Regulation; QH301-705.5; Interleukin-8; Molecular Sequence Data; Endocytosis; Up-Regulation; 3. Good health; Killer Cells, Natural; 03 medical and health sciences; N4i 4: Auto-immunity, transplantation and immunotherapy; Receptors, KIR2DL5; Receptors, KIR; Receptors, KIR2DL4; Solubility; Cytokines; Humans; UMCN 1.4: Immunotherapy, gene therapy and transplantation; Biology (General); Chemokines; Receptors, Immunologic; Research Article; rab5 GTP-Binding Proteins

Signaling from endosomes is emerging as a mechanism by which selected receptors provide sustained signals distinct those generated at the plasma membrane. The activity of natural killer (NK) cells, are important effectors innate immunity and regulators adaptive immunity, controlled primarily that cell surface. Here we show cytokine secretion resting human NK cells induced soluble, but not solid-phase, antibodies to immunoglobulin-like receptor (KIR) 2DL4, for leukocyte antigen (HLA)-G. KIR2DL4 was constitutively internalized into Rab5-positive compartments via dynamin-dependent process. Soluble HLA-G endocytosed KIR2DL4–containing in 293T transfected with KIR2DL4. Chemokine transfection occurred only recombinant forms trafficked endosomes. profile genes up-regulated engagement on revealed proinflammatory/proangiogenic response. similar set cytokines chemokines. This unique stimulation soluble HLA-G, KIR2DL4, implies may useful functions sites expression, such promotion vascularization maternal decidua during early pregnancy.