title: Natural killer cells expressing the KIR2DS1-activating receptor efficiently kill T-cell blasts and dendritic cells: implications in haploidentical HSCT.
abstract: In allogeneic HSCT, NK-cell alloreactivity is determined by the presence in the donor of NK cells expressing inhibitory killer cell Ig-like receptors (KIRs) that recognize HLA class I allotypes present in the donor but lacking in the recipient. Dominant KIR ligands are the C1 and C2 epitopes of HLA-C. All HLA-C allotypes have either the C1 epitope, the ligand for KIR2DL2/L3, or the C2 epitope, the ligand for KIR2DL1/S1. Here, we show that, in alloreactive NK-cell responses, KIR2DS1 expression represents a remarkable advantage as it allows efficient killing of C2/C2 or C1/C2 myelomonocitic dendritic cells (DCs) and T-cell blasts. When DCs or T-cell blasts were derived from C2/C2, Bw4/Bw4 donors, the activating signals delivered by KIR2DS1 could override the inhibition generated by NKG2A or KIR2DL2/L3 expressed on the same NK-cell clone. Furthermore, substantial lysis of C2/C2, Bw4/Bw6 targets was mediated by KIR2DS1(+) NK cells coexpressing KIR3DL1. Importantly, in the case of C1/C2 targets, KIR2DS1(+) NK cells were inhibited by the coexpression of KIR2DL2/L3 but not of NKG2A. Thus, KIR2DS1 expression in HSC donors may substantially increase the size of the alloreactive NK-cell subset leading to an enhanced ability to limit GVHD and improve engrafment.
authors.affiliation: DI.ME.S. Dipartimento di Medicina Sperimentale and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Genova, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Sivori
authors.forename: Simona
authors.initials: S
authors.lastname: Carlomagno
authors.forename: Michela
authors.initials: M
authors.lastname: Falco
authors.forename: Elisa
authors.initials: E
authors.lastname: Romeo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
mesh_terms: D002999:Clone Cells; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: C496212:KIR2DS1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054340:Receptors, KIR