Web of Science: 2 cites, Scopus: 5 cites, Google Scholar: cites,
Differential Immunodominance Hierarchy of CD8 + T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection
Adland, Emily
Hill, Matilda
Lavandier, Nora
Csala, Anna
Edwards, Anne
Chen, Fabian
Radkowski, Marek
Kowalska, Justyna D.
Paraskevis, Dimitrios
Hatzakis, Angelos
Valenzuela-Ponce, Humberto
Pfafferott, Katja
Williams, Ian
Pellegrino, Pierre
Borrow, Persephone
Mori, Masahiko
Rockstroh, Jürgen
Prado, Julia G. (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Mothe, Beatriz (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Dalmau, Judith (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Martinez-Picado, Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Tudor-Williams, Gareth
Frater, John
Stryhn, Anette
Buus, Soren
Teran, Gustavo Reyes
Mallal, Simon
John, Mina
Buchbinder, Susan
Kirk, Gregory
Martin, Jeffrey
Michael, Nelson
Fellay, Jacques
Deeks, Steve
Walker, Bruce
Avila-Rios, Santiago
Cole, David
Brander, Christian (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Carrington, Mary
Goulder, Philip
Universitat Autònoma de Barcelona

Data: 2018
Resum: The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8 + T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8 + T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8 + T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8 + T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8 + T-cell responses that dominate HIV-specific CD8 + T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV. IMPORTANCE CD8 + T cells play a central role in successful control of HIV infection and have the potential also to mediate the eradication of viral reservoirs of infection. The principal means by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01, slow HIV disease progression is believed to be via the particular HIV-specific CD8 + T cell responses restricted by those alleles. We focus here on HLA-B*27:05, one of the best-characterized protective HLA molecules, and the closely related HLA-B*27:02, which differs by only 3 amino acids and which has not been well studied in relation to control of HIV infection. We show that HLA-B*27:02 is also protective against HIV disease progression, but the CD8 + T-cell immunodominance hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8 + T-cell activity in HLA-B*27:05-positive subjects.
Nota: Altres ajuts: This work was funded by grants from the National Institutes of Health (RO1AI46995 to P.G.) and the Wellcome Trust (WT104748MA to P.G.). This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research under contract no. HHSN261200800001E (to M.C.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), U01-AI35042 (Johns Hopkins University Bloomberg School of Public Health; Joseph Margolick, rincipal investigator [PI]), U01-AI35039 (Northwestern University; Steven Wolinsky, PI), U01-AI35040 (University of California, Los Angeles; Roger Detels and Oto Martinez, multiple principal investigators [MPI]), U01-AI35041 (University of Pittsburgh; Charles Rinaldo, PI), and UM1-AI35043 (Johns Hopkins University Bloomberg School of Public Health; Lisa Jacobson, PI). The SCOPE cohort was supported by the UCSF/Gladstone Institute of Virology and Immunology CFAR (P30 AI027763) and the CFAR Network of Integrated Systems (R24 AI067039). Additional support was provided by the Delaney AIDS Research Enterprise (DARE; AI096109 and A127966) and the amfAR Institute for HIV Cure Research (amfAR 109301). P.B. is a Jenner Investigator. I.W. and P.P. are funded by MRC Programme grant MR/K012037.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: article ; recerca ; publishedVersion
Matèria: CD8 + T cell ; HIV Gag ; HIV Nef ; HLA ; HLA-B*27 ; Human immunodeficiency virus
Publicat a: Journal of Virology, Vol. 92 (january 2018) , ISSN 1098-5514

DOI: 10.1128/JVI.01685-17
PMID: 29167337


14 p, 2.0 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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 Registre creat el 2018-03-06, darrera modificació el 2021-03-21



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