학술논문
Incoming HIV virion-derived Gag Spacer Peptide 2 (p1) is a target of effective CD8+T cell antiviral responses
Document Type
Article
Author
Yang, Hongbing; Llano, Anuska; Cedeño, Samandhy; von Delft, Annette; Corcuera, Angelica; Gillespie, Geraldine M.; Knox, Andrew; Leneghan, Darren B.; Frater, John; Stöhr, Wolfgang; Fidler, Sarah; Mothe, Beatriz; Mak, Johnson; Brander, Christian; Ternette, Nicola; Dorrell, Lucy; Sandström, Eric; Darbyshire, Janet; Post, Frank; Conlon, Christopher; Anderson, Jane; Maini, Mala; Peto, Timothy; Sasieni, Peter; Miller, Veronica; Weller, Ian; Fidler, Sarah; Frater, John; Babiker, Abdel; Stöhr, Wolfgang; Pett, Sarah; Dorrell, Lucy; Pace, Matthew; Olejniczak, Natalia; Brown, Helen; Robinson, Nicola; Kopycinski, Jakub; Yang, Hongbing; Hanke, Tomáš; Crook, Alison; Kaye, Steven; McClure, Myra; Erlwein, Otto; Lovell, Andrew; Khan, Maryam; Gabrielle, Michelle; Bennett, Rachel; Sy, Aminata; Gregory, Adam; Hudson, Fleur; Russell, Charlotte; Wood, Gemma; Box, Hanna; Kingsley, Cherry; Topping, Katie; Lever, Andrew; Wills, Mark; Fun, Axel; Bandara, Mikaila; Kelly, Damian; Collins, Simon; Markham, Alex; Rauchenberger, Mary; Sowunmi, Yinka; Shidfar, Shaadi; Hague, Dominic; Nelson, Mark; Cerrone, Maddalena; Castrillo Martinez, Nadia; Barber, Tristan; Schoolmeesters, Alexandra; Weaver, Christine; Thunder, Orla; Rowlands, Jane; Higgs, Christopher; Fedele, Serge; Bracchi, Margherita; Thomas, Lervina; Bourke, Peter; Nwokolo, Nneka; Lawrenson, Gaynor; Fiorino, Marzia; Lukha, Hinal; Kinloch-de Loes, Sabine; Johnson, Margaret; Nightingale, Alice; Ngwu, Nnenna; Byrne, Patrick; Cuthbertson, Zoe; Jones, Martin; Fernandez, Tina; Clarke, Amanda; Fisher, Martin; Gleig, Rebecca; Trevitt, Vittorio; Fitzpatrick, Colin; Adams, Tanya; Finnerty, Fiounnuala; Thornhill, John; Lewis, Heather; Kuldanek, Kristin; Fox, Julie; Lwanga, Julianne; Uzu, Hiromi; Lee, Ming; Merle, Simon; O’Rourke, Patrick; Jendrulek, Isabel; Zarko Flynn, Taras; Taylor, Mark; Manuel Tiraboschi, Juan; Murray, Tammy
Source
Cell Reports; May 2021, Vol. 35 Issue: 6
Subject
Language
ISSN
22111247
Abstract
Persistence of HIV through integration into host DNA in CD4+T cells presents a major barrier to virus eradication. Viral integration may be curtailed when CD8+T cells are triggered to kill infected CD4+T cells through recognition of histocompatibility leukocyte antigen (HLA) class I-bound peptides derived from incoming virions. However, this has been reported only in individuals with “beneficial” HLA alleles that are associated with superior HIV control. Through interrogation of the pre-integration immunopeptidome, we obtain proof of early presentation of a virion-derived HLA-A∗02:01-restricted epitope, FLGKIWPSH (FH9), located in Gag Spacer Peptide 2 (SP2). FH9-specific CD8+T cell responses are detectable in individuals with primary HIV infection and eliminate HIV-infected CD4+T cells prior to virus production in vitro. Our data show that non-beneficial HLA class I alleles can elicit an effective antiviral response through early presentation of HIV virion-derived epitopes and also demonstrate the importance of SP2 as an immune target.