title: Uptake of CCR7 by KIR2DS4⁺ NK cells is induced upon recognition of certain HLA-C alleles.
abstract: The KIR2DS4 receptor is the oldest KIR2DS expressed by human NK lymphocytes. The specificity of recognition of this receptor for various HLA class I alleles has been demonstrated; however it remains poorly understood whether these interactions may result in the activation of some specific functions in NK cells. Here, we examined the functional outcome of the KIR2DS4/HLA class I interaction by the use of an alternative functional system based on the ability of KIR2DS4 to regulate the mechanism of trogocytosis by NK cells. We demonstrate that KIR2DS4 can induce the uptake of CCR7 by KIR2DS4(+) NKG2A(+) NK cell clones after interacting with CCR7(+) target cells expressing HLA-Cw4 and HLA-Cw6 alleles. However this interaction is not always sufficient to override the inhibition generated by NKG2A expressed on the same NK cells. The recognition of HLA-Cw4 was confirmed by experiments of cytotoxicity against HLA-C-transfected cells. We also show that, different from resting NK cells, the acquisition of CCR7 in response to IL-18 cannot occur in IL2-activated NK cells because of a marked downregulation in their IL-18Rα expression. As a consequence trogocytosis represents the major mechanism by which KIR2DS4(+) activated NK cells acquire the expression of this chemokine receptor.
authors.affiliation: Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pesce
authors.affiliation: Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Carlomagno
authors.affiliation: Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, Italy ; Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Viale Benedetto XV 9, 16132 Genova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.affiliation: Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, Italy ; Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Viale Benedetto XV 9, 16132 Genova, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Sivori
authors.affiliation: Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, Italy ; Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Viale Benedetto XV 9, 16132 Genova, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
mesh_terms: D002461:Cell Line, Transformed; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020382:Interleukin-18 / Q000378:metabolism; D053727:Interleukin-18 Receptor alpha Subunit / Q000096:biosynthesis; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism; D021381:Protein Transport; D054400:Receptors, CCR7 / Q000378:metabolism*; D054340:Receptors, KIR / Q000378:metabolism*
chemical_list: C515370:CCR7 protein, human; D015236:HLA-C Antigens; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D007376:Interleukin-2; C473953:KIR2DS4 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054400:Receptors, CCR7; D054340:Receptors, KIR