{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T04:25:34Z","timestamp":1750998334889,"version":"3.40.5"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008433","name":"Consejer\u00eda de Educaci\u00f3n, Juventud y Deporte, Comunidad de Madrid","doi-asserted-by":"publisher","award":["SAF2016\u201080363\u2010C2\u2010 2\u2010R"],"award-info":[{"award-number":["SAF2016\u201080363\u2010C2\u2010 2\u2010R"]}],"id":[{"id":"10.13039\/501100008433","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["GCB15152947MELE"],"award-info":[{"award-number":["GCB15152947MELE"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008433","name":"Consejer\u00eda de Educaci\u00f3n, Juventud y Deporte, Comunidad de Madrid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008433","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HLA"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:p>NK cells monitor altered molecular patterns in tumors and infected cells through an ample array of receptors. Two families of evolutionarily distant receptors have converged to enable human NK cells to sense levels of HLA class I ligands, frequently abnormal in altered cells. Whilst different forms of polymorphism are a hallmark of killer\u2010cell immunoglobulin\u2010like receptors and their classic HLA\u2010A, B, and C ligands, genetic diversity of killer\u2010cell lectin\u2010like receptors for the non\u2010classical HLA\u2010E (CD94\/NKG2 heterodimers) is less conspicuous and has attracted less attention. A common pattern of diversification in both receptor families is evolution of pairs of inhibitory and activating homologs for a common ligand, the genes encoding activating receptors being more frequently affected by copy number variation (CNV). This is exemplified by the gene encoding the activating NKG2C subunit (<jats:italic>KLRC2<\/jats:italic> or <jats:italic>NKG2C<\/jats:italic>), which marks an NK\u2010cell subpopulation that differentiates or expands in response to cytomegalovirus. We have studied <jats:italic>NKG2C<\/jats:italic> diversity in 240 South European individuals, using polymerase chain reaction and sequencing methods to assess both gene CNV and single\u2010nucleotide polymorphisms (SNPs) affecting its promoter, coding and 3\u2032\u2010untranslated (3\u2032UT) regions. Sequence analysis revealed eight common SNPs\u2014one in the promoter, two in the coding sequence, and five in the 3\u2032UT region. These SNPs associate strongly with each other, forming three conserved extended haplotypes (frequencies: 0.456, 0.221, and 0.117). Homo\u2010 and heterozygous combination of these, together with complete gene deletion (0.175) and additional haplotypes with frequencies lower than 0.015, generate a diversity of <jats:italic>NKG2C<\/jats:italic> genotypes of potential immunological importance.<\/jats:p>","DOI":"10.1111\/tan.14734","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T15:19:29Z","timestamp":1657293569000},"page":"469-478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Diversity of <scp><i>NKG2C<\/i><\/scp> genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3\u2032\u2010untranslated regions"],"prefix":"10.1111","volume":"100","author":[{"given":"Judit","family":"Asenjo","sequence":"first","affiliation":[{"name":"Immunogenetics and Histocompatibility Lab Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro \u2010 Segovia de Arana  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Moraru","sequence":"additional","affiliation":[{"name":"Immunogenetics and Histocompatibility Lab Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro \u2010 Segovia de Arana  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karima","family":"Al\u2010Akioui\u2010Sanz","sequence":"additional","affiliation":[{"name":"Immunogenetics and Histocompatibility Lab Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro \u2010 Segovia de Arana  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3118-8654","authenticated-orcid":false,"given":"Mireia","family":"Altadill","sequence":"additional","affiliation":[{"name":"Medicine and Life Sciences University Pompeu Fabra  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aura","family":"Muntasell","sequence":"additional","affiliation":[{"name":"Immunology, Department of Pathology Hospital del Mar Medical Research Institute (IMIM)  Barcelona Spain"},{"name":"Department of Cell Biology, Physiology and Immunology Universitat Auton\u00f2ma de Barcelona  Bellaterra Catalonia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"L\u00f3pez\u2010Botet","sequence":"additional","affiliation":[{"name":"Medicine and Life Sciences University Pompeu Fabra  Barcelona Spain"},{"name":"Immunology, Department of Pathology Hospital del Mar Medical Research Institute (IMIM)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0300-9225","authenticated-orcid":false,"given":"Carlos","family":"Vilches","sequence":"additional","affiliation":[{"name":"Immunogenetics and Histocompatibility Lab Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro \u2010 Segovia de Arana  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_2_1","DOI":"10.1084\/jem.20042558"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_1","DOI":"10.1034\/j.1600-065X.2001.1810106.x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_1","DOI":"10.1146\/annurev.immunol.20.092501.134942"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_1","DOI":"10.1038\/35869"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_1","DOI":"10.1073\/pnas.95.9.5199"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_1","DOI":"10.1084\/jem.188.10.1841"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_1","DOI":"10.1002\/eji.1830270230"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_1","DOI":"10.1126\/science.287.5455.1031"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_1","DOI":"10.4049\/jimmunol.164.10.5019"},{"doi-asserted-by":"publisher","key":"e_1_2_10_11_1","DOI":"10.1038\/s41590-018-0082-6"},{"doi-asserted-by":"publisher","key":"e_1_2_10_12_1","DOI":"10.1126\/science.1070884"},{"doi-asserted-by":"publisher","key":"e_1_2_10_13_1","DOI":"10.1073\/pnas.092258599"},{"doi-asserted-by":"publisher","key":"e_1_2_10_14_1","DOI":"10.1182\/blood-2004-05-2058"},{"doi-asserted-by":"publisher","key":"e_1_2_10_15_1","DOI":"10.1016\/j.smim.2014.03.002"},{"key":"e_1_2_10_16_1","first-page":"298","article-title":"Modulation of human leukocyte antigen\u2010C by human cytomegalovirus stimulates KIR2DS1 recognition by natural killer cells","volume":"8","author":"Ploeg K","year":"2017","journal-title":"Front Immunol"},{"doi-asserted-by":"publisher","key":"e_1_2_10_17_1","DOI":"10.1111\/imr.12318"},{"doi-asserted-by":"publisher","key":"e_1_2_10_18_1","DOI":"10.3389\/fimmu.2019.00177"},{"doi-asserted-by":"publisher","key":"e_1_2_10_19_1","DOI":"10.1093\/nar\/gks1140"},{"issue":"6","key":"e_1_2_10_20_1","first-page":"295","article-title":"Isolation and characterization of NK cell or NK\/T cell\u2010specific cDNA clones","volume":"4","author":"Houchins JP","year":"1990","journal-title":"J Mol Cell Immunol"},{"doi-asserted-by":"publisher","key":"e_1_2_10_21_1","DOI":"10.1007\/s002510050276"},{"doi-asserted-by":"publisher","key":"e_1_2_10_22_1","DOI":"10.1038\/sj.gene.6363940"},{"doi-asserted-by":"publisher","key":"e_1_2_10_23_1","DOI":"10.1093\/intimm\/dxh013"},{"doi-asserted-by":"publisher","key":"e_1_2_10_24_1","DOI":"10.4049\/jimmunol.1103434"},{"doi-asserted-by":"publisher","key":"e_1_2_10_25_1","DOI":"10.1002\/eji.201343773"},{"doi-asserted-by":"publisher","key":"e_1_2_10_26_1","DOI":"10.1111\/j.1399-0039.2007.00907.x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_27_1","DOI":"10.4049\/jimmunol.168.1.240"},{"doi-asserted-by":"publisher","key":"e_1_2_10_28_1","DOI":"10.1002\/(SICI)1521-4141(199801)28:01<327::AID-IMMU327>3.0.CO;2-O"},{"doi-asserted-by":"publisher","key":"e_1_2_10_29_1","DOI":"10.1111\/j.1399-0039.2012.01911.x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_30_1","DOI":"10.1111\/tan.14231"},{"doi-asserted-by":"publisher","key":"e_1_2_10_31_1","DOI":"10.4049\/jimmunol.1502438"},{"doi-asserted-by":"publisher","key":"e_1_2_10_32_1","DOI":"10.1074\/jbc.M208268200"},{"doi-asserted-by":"publisher","key":"e_1_2_10_33_1","DOI":"10.3389\/fimmu.2018.00390"},{"issue":"7","key":"e_1_2_10_34_1","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.4049\/jimmunol.162.7.3996","article-title":"Triggering of effector functions on a CD8+ T cell clone upon the aggregation of an activatory CD94\/kp39 heterodimer","volume":"162","author":"Bell\u00f3n T","year":"1999","journal-title":"J Immunol"},{"doi-asserted-by":"publisher","key":"e_1_2_10_35_1","DOI":"10.1016\/S1074-7613(00)80394-5"},{"doi-asserted-by":"publisher","key":"e_1_2_10_36_1","DOI":"10.1093\/nar\/gkh372"},{"doi-asserted-by":"publisher","key":"e_1_2_10_37_1","DOI":"10.1038\/nprot.2011.409"},{"doi-asserted-by":"publisher","key":"e_1_2_10_38_1","DOI":"10.1002\/humu.21209"},{"doi-asserted-by":"publisher","key":"e_1_2_10_39_1","DOI":"10.1016\/j.cell.2006.07.031"},{"doi-asserted-by":"publisher","key":"e_1_2_10_40_1","DOI":"10.1073\/pnas.0802736105"},{"doi-asserted-by":"publisher","key":"e_1_2_10_41_1","DOI":"10.1084\/jem.20072525"},{"doi-asserted-by":"publisher","key":"e_1_2_10_42_1","DOI":"10.1016\/j.immuni.2007.10.013"}],"container-title":["HLA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tan.14734","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/tan.14734","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tan.14734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T04:28:31Z","timestamp":1692678511000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/tan.14734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,20]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1111\/tan.14734"],"URL":"https:\/\/doi.org\/10.1111\/tan.14734","archive":["Portico"],"relation":{},"ISSN":["2059-2302","2059-2310"],"issn-type":[{"type":"print","value":"2059-2302"},{"type":"electronic","value":"2059-2310"}],"subject":[],"published":{"date-parts":[[2022,7,20]]},"assertion":[{"value":"2022-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}