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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Differential immunodominance hierarchy of CD8+ T-cell responses in HLA-B*27:05- and -B*27:02-mediated control of HIV-1 infection
Journal of Virology, Volume 92, No. 4, Article e01685-17, Year 2018
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Description
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 HLAB* 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 HLAB* 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. © 2018 American Society for Microbiology.
Authors & Co-Authors
Adland, Emily
United Kingdom, Oxford
University of Oxford
Csala, Anna
United Kingdom, Oxford
University of Oxford
Edwards, Anne R.
United Kingdom, Oxford
Oxford University Hospitals Nhs Foundation Trust
Chen, Fabian
United Kingdom, Reading
Royal Berkshire Hospital
Kowalska, Justyna Dominika
Poland, Warsaw
Sp Zoz Wojewódzki Szpital Zakazny - Centrum Diagnostyki I Terapii Aids, Warszawa
Paraskevis, D. N.
Greece, Athens
National and Kapodistrian University of Athens
Hatzakis, Angelos E.
Greece, Athens
National and Kapodistrian University of Athens
Valenzuela-Ponce, Humberto
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Pfafferott, Katja J.
United Kingdom, Oxford
University of Oxford
Williams, Ian G.
United Kingdom, London
University College London
Pellegrino, Pierre
United Kingdom, London
University College London
Borrow, Persephone
United Kingdom, Oxford
University of Oxford
Mori, Masahiko
United Kingdom, Oxford
University of Oxford
Rockstroh, Jürgen Kurt
Germany, Bonn
Universitätsklinikum Bonn
Prado, Julia Garcia
Spain, Badalona
Fundació Institut Dinvestigació en Ciències de la Salut Germans Trias I Pujol
Mothe, Beatriz
Spain, Badalona
Fundació Institut Dinvestigació en Ciències de la Salut Germans Trias I Pujol
Spain, Vic
Universitat de Vic - Universitat Central de Catalunya Uvic-ucc
Dalmau, Judith
Spain, Badalona
Fundació Institut Dinvestigació en Ciències de la Salut Germans Trias I Pujol
Martínez-Picado, Javier
Spain, Badalona
Fundació Institut Dinvestigació en Ciències de la Salut Germans Trias I Pujol
Spain, Vic
Universitat de Vic - Universitat Central de Catalunya Uvic-ucc
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Tudor-Williams, Gareth
United Kingdom, London
Imperial College London
Frater, John
United Kingdom, Oxford
University of Oxford
Stryhn, Anette
Denmark, Copenhagen
Københavns Universitet
Buus, Soren
Denmark, Copenhagen
Københavns Universitet
Teran, Gustavo Reyes
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Mallal, Simon Alexander
United States, Nashville
Vanderbilt University Medical Center
John, Mina
Australia, Perth
Murdoch University
Buchbinder, Susan P.
United States, San Francisco
San Francisco Department of Public Health
Kirk, Gregory D.
United States, Baltimore
Johns Hopkins University
Martin, Jeffrey N.
United States, San Francisco
University of California, San Francisco
Michael, Nelson L.
United States, Silver Spring
Walter Reed Army Institute of Research
Fellay, Jacques
Switzerland, Lausanne
École Polytechnique Fédérale de Lausanne
Deeks, Steven G.
United States, Nashville
Vanderbilt University Medical Center
Walker, Bruce D.
United States, Boston
Massachusetts General Hospital
Ávila-Ríos, Santiago
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Cole, David K.
United Kingdom, Cardiff
Cardiff University School of Medicine
Brander, Christian
Spain, Badalona
Fundació Institut Dinvestigació en Ciències de la Salut Germans Trias I Pujol
Spain, Vic
Universitat de Vic - Universitat Central de Catalunya Uvic-ucc
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Carrington, Mary N.
United States, Boston
Massachusetts General Hospital
United States, Reston
Leidos Inc.
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
University of Oxford
Statistics
Citations: 14
Authors: 37
Affiliations: 23
Identifiers
Doi:
10.1128/JVI.01685-17
ISSN:
0022538X
Research Areas
Genetics And Genomics
Infectious Diseases