{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nKIR3DS1 is a conserved activating receptor expressed on natural killer (NK) cells that, despite being encoded in a locus also containing inhibitory KIR3DL1 alleles, is reliably detectable on fresh circulating NK cells. Experimental transfection studies have demonstrated that surface expression of KIR3DS1 depends on its association with the adaptor protein DAP12, and population analyses indicate that its sequence has been maintained by balancing selection alongside inhibitory counterparts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional studies in the context of viral infections have shown that KIR3DS1-expressing NK cells are endowed with enhanced antiviral effector potential. In vitro experiments using HIV-1 target cells expressing the putative ligand HLA-Bw4‐80I demonstrate that NK cells carrying KIR3DS1 exhibit marked, dose‐ and cell–contact–dependent inhibition of viral replication, along with increased secretion of interferon-γ. These observations underscore the receptor’s role in promoting early antiviral responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond baseline antiviral functions, the KIR3DS1 receptor appears to contribute to the dynamic adaptation of the NK-cell compartment during acute viral infections. In acute HIV-1 infection, for instance, expansion of NK cells expressing KIR3DS1 has been observed, suggesting that the receptor may help tailor immune responses to rapidly evolving viral challenges. In the setting of hematopoietic stem cell transplantation for hematological malignancies, donor KIR3DS1 positivity correlates with a reduction in acute graft-versus-host disease, implicating the receptor in modulating the balance between beneficial graft-versus-tumor effects and deleterious alloreactivity. Moreover, during cytomegalovirus (CMV) infection, KIR3DS1—along with other activating KIRs—contributes to the clonal-like expansion of NK cells, further supporting its role in antiviral immunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent data have also extended the functional relevance of KIR3DS1 to hepatitis C virus (HCV) infection. In well‐designed cell culture models, humanized mice, and primary liver tissues derived from individuals with HCV, the ligand HLA-F is up-regulated on infected cells, and engagement of KIR3DS1 with HLA-F appears to potentiate NK cell–mediated antiviral control. This finding opens avenues to develop strategies that promote KIR3DS1/HLA-F interactions to enhance immune defenses against chronic viral infections and possibly malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anita Trundley, Helge Frebel, Des Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Allelic expression patterns of KIR3DS1 and 3DL1 using the Z27 and DX9 antibodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.200636773"}], "href": "https://doi.org/10.1002/eji.200636773"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17301953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17301953"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Paul J Norman, Laurent Abi-Rached, Ketevan Gendzekhadze, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng2111"}], "href": "https://doi.org/10.1038/ng2111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17694054"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17694054"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Galit Alter, Maureen P Martin, Nickolas Teigen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20070695"}], "href": "https://doi.org/10.1084/jem.20070695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18025129"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18025129"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Brian R Long, Lishomwa C Ndhlovu, Jorge R Oksenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Conferral of enhanced natural killer cell function by KIR3DS1 in early human immunodeficiency virus type 1 infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.02449-07"}], "href": "https://doi.org/10.1128/JVI.02449-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18305035"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18305035"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Roberto Díaz-Peña, Miguel Angel Blanco-Gelaz, Beatriz Suárez-Alvarez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activating KIR genes are associated with ankylosing spondylitis in Asian populations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humimm.2008.04.012"}], "href": "https://doi.org/10.1016/j.humimm.2008.04.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18638658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18638658"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Galit Alter, Suzannah Rihn, Katharine Walter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HLA class I subtype-dependent expansion of KIR3DS1+ and KIR3DL1+ NK cells during acute human immunodeficiency virus type 1 infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00256-09"}], "href": "https://doi.org/10.1128/JVI.00256-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19386717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19386717"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jeffrey M Venstrom, Ted A Gooley, Stephen Spellman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Donor activating KIR3DS1 is associated with decreased acute GVHD in unrelated allogeneic hematopoietic stem cell transplantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-08-236943"}], "href": "https://doi.org/10.1182/blood-2009-08-236943"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20124216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20124216"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Vivien Béziat, Lisa L Liu, Jenny-Ann Malmberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-10-459545"}], "href": "https://doi.org/10.1182/blood-2012-10-459545"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23325834"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23325834"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sebastian Lunemann, Anja Schöbel, Janine Kah, et al. 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