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Incoming HIV virion-derived Gag Spacer Peptide 2 (p1) is a target of effective CD8+ T cell antiviral responses

2021; Cell Press; Volume: 35; Issue: 6 Linguagem: Inglês

10.1016/j.celrep.2021.109103

2639-1856

Hongbing Yang, Anuska Llano, Samandhy Cedeño, Annette von Delft, Angelica Corcuera, Geraldine M. Gillespie, Andrew Knox, Darren B. Leneghan, John Frater, Wolfgang Stöhr, Sarah Fidler, Beatriz Mothe, Johnson Mak, Christian Brander, Nicola Ternette, Lucy Dorrell, Eric Sandström, Janet Darbyshire, Frank A. Post, Christopher P. Conlon, Jane Anderson, Mala K. Maini, Timothy Peto, Peter Sasieni, Veronica Miller, Ian Weller, Sarah Fidler, John Frater, Abdel Babiker, Wolfgang Stöhr, Sarah Pett, Lucy Dorrell, Matthew Pace, Natalia Olejniczak, Helen Brown, Nicola Robinson, Jakub Kopycinski, Hongbing Yang, Tomáš Hanke, Alison Crook, Steven Kaye, Myra O. McClure, Otto Erlwein, Andrew Lovell, Maryam Khan, Michelle Gabrielle, Rachel Bennett, Aminata Sy, Adam Gregory, Fleur Hudson, Charlotte Russell, Gemma Wood, Hanna Box, Cherry Kingsley, Katie Topping, Andrew Lever, Mark R. Wills, Axel Fun, Mikaila Bandara, Damian J. Kelly, Simon Collins, Alex Markham, Mary Rauchenberger, Yinka Sowunmi, Shaadi Shidfar, Dominic Hague, Mark Nelson, Maddalena Cerrone, Nadia Castrillo Martinez, Tristan Barber, Alexandra Schoolmeesters, Christine Weaver, Orla Thunder, Jane Rowlands, Chris Higgs, Serge Fedele, Margherita Bracchi, Lervina Thomas, Peter Bourke, Nneka Nwokolo, Gaynor Lawrenson, Marzia Fiorino, Hinal Lukha, Sabine Kinloch-de Loës, Margaret M. Johnson, Alice Nightingale, Nnenna Ngwu, P. S. Byrne, Zoe Cuthbertson, Martin Jones, Tina Fernandez, Amanda Clarke, Martin Fisher, Rebecca Gleig, Vittorio Trevitt, Colin Fitzpatrick, Tanya Adams, Fiounnuala Finnerty, John Thornhill, Heather Lewis, Kristin Kuldanek, Julie Fox, Julianne Lwanga, Hiromi Uzu, Ming Lee, S Merle, Patrick O’Rourke, Isabel Jendrulek, T Flynn, Mark A. Taylor, Juan Tiraboschi, Tammy Murray,

vaccines and immunoinformatics approaches

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.