학술논문
Differential Immunodominance Hierarchy of CD8 + T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection.
Document Type
Academic Journal
Author
Adland E; Department of Paediatrics, University of Oxford, United Kingdom.; Hill M; Department of Paediatrics, University of Oxford, United Kingdom.; Lavandier N; Department of Paediatrics, University of Oxford, United Kingdom.; Csala A; Department of Paediatrics, University of Oxford, United Kingdom.; Edwards A; Department of GU Medicine, The Churchill Hospital, Oxford University NHS Foundation Trust, Oxford, United Kingdom.; Chen F; Department of Sexual Health, Royal Berkshire Hospital, Reading, United Kingdom.; Radkowski M; Department of Immunopathology of Infectious and Parasitic Diseases, Hospital for Infectious Diseases, Medical University of Warsaw, Warsaw, Poland.; Kowalska JD; Department of Immunopathology of Infectious and Parasitic Diseases, Hospital for Infectious Diseases, Medical University of Warsaw, Warsaw, Poland.; Paraskevis D; Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Hatzakis A; Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Valenzuela-Ponce H; Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.; Pfafferott K; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Williams I; Centre for Sexual Health and HIV Research, Mortimer Market Centre, London, United Kingdom.; Pellegrino P; Centre for Sexual Health and HIV Research, Mortimer Market Centre, London, United Kingdom.; Borrow P; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Mori M; Department of Paediatrics, University of Oxford, United Kingdom.; Rockstroh J; Department of Medicine I, University Hospital Bonn, Bonn, Germany.; Prado JG; AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona, Badalona, Spain.; Mothe B; AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona, Badalona, Spain.; University of Vic-Central University of Catalonia (UVic-UCC), Vic, Barcelona, Spain.; Dalmau J; AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona, Badalona, Spain.; Martinez-Picado J; AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona, Badalona, Spain.; University of Vic-Central University of Catalonia (UVic-UCC), Vic, Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.; Tudor-Williams G; Department of Paediatrics, Imperial College, London, United Kingdom.; Frater J; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Oxford Martin School, University of Oxford, Oxford, United Kingdom.; Stryhn A; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.; Buus S; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.; Teran GR; Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.; Mallal S; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; John M; Institute of Immunology and Infectious Diseases, Murdoch University, Perth, Australia.; Buchbinder S; San Francisco Department of Public Health, HIV Research Section, San Francisco, California, USA.; Kirk G; Department of Epidemiology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, USA.; Martin J; Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.; Michael N; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Fellay J; School of Life Sciences, EPFL, Lausanne, Switzerland.; Deeks S; San Francisco Department of Public Health, HIV Research Section, San Francisco, California, USA.; Walker B; Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, USA.; Avila-Rios S; Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.; Cole D; Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom.; Immunocore Limited, Abingdon, Oxfordshire, United Kingdom.; Brander C; AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona, Badalona, Spain.; University of Vic-Central University of Catalonia (UVic-UCC), Vic, Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.; Carrington M; Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, USA.; Cancer and Inflammation Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Maryland, USA.; Goulder P; Department of Paediatrics, University of Oxford, United Kingdom philip.goulder@paediatrics.ox.ac.uk.
Source
Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(Copyright © 2018 Adland et al.)
(Copyright © 2018 Adland et al.)