{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:51:26Z","timestamp":1790085086436,"version":"4.0.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,10,24]],"date-time":"2013-10-24T00:00:00Z","timestamp":1382572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI071906"],"award-info":[{"award-number":["R01 AI071906"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UAB Center for AIDS Research","award":["P30 AI027767"],"award-info":[{"award-number":["P30 AI027767"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,24]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>As a mechanism of self-protection, signal peptides cleaved from human leukocyte antigen (HLA) class I products bind to HLA-E before the complex interacts with the natural killer (NK) cell receptor CD94\/NKG2A to inhibit NK-mediated cell lysis. Two types of the signal peptides differ in their position 2 (P2) anchor residue, with P2-methionine (P2-M) having higher HLA-E binding affinity than P2-threonine (P2-T). All HLA-A and HLA-C molecules carry P2-M, whereas HLA-B products have either P2-M or P2-T. Epidemiological evidence suggests that P2-M is unfavourable in the context of HIV-1 infection, being associated with accelerated acquisition of HIV-1 infection in two African cohorts. To begin elucidating the functional mechanism, we studied NK-mediated killing of CD4+ T cells and monocyte-derived macrophages infected with two laboratory-adapted HIV-1 strains and two transmitted\/founder (T\/F) viruses. In the presence of target cells derived from individuals with the three HLA-B P2 genotypes (M\/M, M\/T and T\/T), NK-mediated cytolysis was elevated consistently for P2-T in a dose-dependent manner for all cell and virus combinations tested (P\u2009=\u20090\u00b7008\u20130\u00b703). Treatment of target cells with an anti-HLA-E monoclonal antibody restored NK-mediated cytolysis of cells expressing P2-M. Observations on cell lysis were also substantiated by measurements of HIV-1 p24 antigen in the culture supernatants. Overall, our experiments indicate that the anti-HIV-1 function mediated by NK cells is compromised by P2-M, corroborating the association of HLA-B genotype encoding P2-M with accelerated HIV-1 acquisition.<\/jats:p>","DOI":"10.1111\/cei.12187","type":"journal-article","created":{"date-parts":[[2013,8,19]],"date-time":"2013-08-19T01:09:16Z","timestamp":1376874556000},"page":"414-423","source":"Crossref","is-referenced-by-count":43,"title":["Dimorphic HLA-B signal peptides differentially influence HLA-E- and natural killer cell-mediated cytolysis of HIV-1-infected target cells"],"prefix":"10.1093","volume":"174","author":[{"given":"A M","family":"Merino","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"},{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Sabbaj","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Easlick","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Goepfert","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A","family":"Kaslow","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"},{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA"},{"name":"Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA"},{"name":"Department of Veterans Affairs, Washington, DC, 20420, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA"},{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,10,24]]},"reference":[{"key":"2021122009582346100_cei12187-bib-0001","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/embor.2009.203","article-title":"Hidden talents of natural killers: NK cells in innate and adaptive immunity","volume":"10","author":"Cooper","year":"2009","journal-title":"EMBO 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