title: Transfer of the human NKG2D ligands UL16 binding proteins (ULBP) 1-3 is related to lytic granule release and leads to ligand retransfer and killing of ULBP-recipient natural killer cells.
abstract: After immune interactions, membrane fragments can be transferred between cells. This fast transfer of molecules is transient and shows selectivity for certain proteins; however, the constraints underlying acquisition of a protein are unknown. To characterize the mechanism and functional consequences of this process in natural killer (NK) cells, we have compared the transfer of different NKG2D ligands. We show that human NKG2D ligands can be acquired by NK cells with different efficiencies. The main findings are that NKG2D ligand transfer is related to immune activation and receptor-ligand interaction and that NK cells acquire these proteins during interactions with target cells that lead to degranulation. Our results further demonstrate that NK cells that have acquired NKG2D ligands can stimulate activation of autologous NK cells. Surprisingly, NK cells can also re-transfer the acquired molecule to autologous effector cells during this immune recognition that leads to their death. These data demonstrate that transfer of molecules occurs as a consequence of immune recognition and imply that this process might play a role in homeostatic tuning-down of the immune response or be used as marker of interaction.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Agencia Estatal Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Sheila
authors.initials: S
authors.lastname: López-Cobo
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Agencia Estatal Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Romera-Cárdenas
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Agencia Estatal Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Eva M
authors.initials: EM
authors.lastname: García-Cuesta
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Agencia Estatal Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Hugh T
authors.initials: HT
authors.lastname: Reyburn
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Agencia Estatal Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Valés-Gómez
mesh_terms: D000818:Animals; D016466:CHO Cells; D015550:Cell Degranulation / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D058851:GPI-Linked Proteins / Q000378:metabolism; D017261:Glycosylphosphatidylinositols; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D021381:Protein Transport; D055607:Receptors, Natural Killer Cell / Q000276:immunology
chemical_list: D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D055607:Receptors, Natural Killer Cell; C423231:ULBP1 protein, human; C423230:ULBP2 protein, human; C423229:ULBP3 protein, human
keywords: NKG2D; glycosyl-phosphatidyl-inositol-anchored proteins; human natural killer cells; immune synapse; trogocytosis