{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T06:52:36Z","timestamp":1779173556425,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T00:00:00Z","timestamp":1407801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI50429"],"award-info":[{"award-number":["R01 AI50429"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:p>The acquisition and maintenance of NK\u2010cell function is mediated by inhibitory killer\u2010cell immunoglobulin\u2010like receptors (KIRs) through their interaction with HLA class I molecules. Recently, HLA\u2010C expression levels were shown to be correlated with protection against multiple outcomes of HIV\u20101 infection; however, the underlying mechanisms are poorly understood. As HLA\u2010C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2\/3, we sought to determine whether <jats:italic>HLA\u2010C<\/jats:italic> group haplotypes affect NK\u2010cell responses during primary HIV\u20101 infection. The phenotypes and functional capacity of NK\u00a0cells derived from HIV\u20101\u2010positive and HIV\u20101\u2010negative individuals were assessed (<jats:italic>N<\/jats:italic> = 42 and <jats:italic>N<\/jats:italic> = 40, respectively). HIV\u20101 infection was associated with an increased frequency of KIR2DL1\u20133<jats:sup>+<\/jats:sup> NK\u00a0cells. Further analysis showed that KIR2DL1<jats:sup>+<\/jats:sup> NK\u00a0cells were selectively increased in individuals homozygous for <jats:italic>HLA\u2010C2<\/jats:italic>, while <jats:italic>HLA\u2010C1<\/jats:italic>\u2010homozygous individuals displayed increased proportions of KIR2DL2\/3<jats:sup>+<\/jats:sup> NK\u00a0cells. KIR2DL1\u20133<jats:sup>+<\/jats:sup> NK\u00a0cells were furthermore more polyfunctional during primary HIV\u20101 infection in individuals also encoding for their cognate <jats:italic>HLA\u2010C<\/jats:italic> group haplotypes, as measured by degranulation and IFN\u2010\u03b3 and TNF\u2010\u03b1 production. These results identify a novel relationship between HLA\u2010C and KIR2DL<jats:sup>+<\/jats:sup> NK\u2010cell subsets and demonstrate that HLA\u2010C\u2010mediated licensing modulates NK\u2010cell responses to primary HIV\u20101 infection.<\/jats:p>","DOI":"10.1002\/eji.201444751","type":"journal-article","created":{"date-parts":[[2014,7,10]],"date-time":"2014-07-10T16:41:15Z","timestamp":1405010475000},"page":"2938-2948","source":"Crossref","is-referenced-by-count":38,"title":["Increased frequency and function of KIR2DL1\u20133<sup>+<\/sup> NK\u00a0cells in primary HIV\u20101 infection are determined by <i>HLA\u2010C<\/i> group haplotypes"],"prefix":"10.1002","volume":"44","author":[{"given":"Christian","family":"K\u00f6rner","sequence":"first","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell E.","family":"Granoff","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Molly A.","family":"Amero","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael N.","family":"Sirignano","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sagar A.","family":"Vaidya","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard  Cambridge MA USA"},{"name":"Division of Infectious Diseases Massachusetts General Hospital  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Jost","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard  Cambridge MA 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