Journal ArticleDOI
Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes.
Nicole Frahm,Photini Kiepiela,Sharon Adams,Caitlyn Linde,Hannah S. Hewitt,Kaori Sango,Margaret E. Feeney,Marylyn M. Addo,Mathias Lichterfeld,Matthew P. Lahaie,Eunice Pae,Alysse G. Wurcel,Alysse G. Wurcel,Timothy Roach,M. Anne St. John,Marcus Altfeld,Francesco M. Marincola,Corey Moore,Simon Mallal,Mary Carrington,David Heckerman,Todd M. Allen,James I. Mullins,Bette T. Korber,Bette T. Korber,Philip J. R. Goulder,Philip J. R. Goulder,Bruce D. Walker,Bruce D. Walker,Christian Brander +29 more
TLDR
Analysis of cytotoxic T lymphocyte responses restricted by HLA-B*1503 suggests that subdominant responses can contribute to in vivo viral control and that high HLA allele frequencies may drive the elimination ofSubdominant yet effective epitopes from circulating viral populations.Abstract:
Despite limited data supporting the superiority of dominant over subdominant responses, immunodominant epitopes represent the preferred vaccine candidates. To address the function of subdominant responses in human immunodeficiency virus infection, we analyzed cytotoxic T lymphocyte responses restricted by HLA-B*1503, a rare allele in a cohort infected with clade B, although common in one infected with clade C. HLA-B*1503 was associated with reduced viral loads in the clade B cohort but not the clade C cohort, although both shared the immunodominant response. Clade B viral control was associated with responses to several subdominant cytotoxic T lymphocyte epitopes, whereas their clade C variants were less well recognized. These data suggest that subdominant responses can contribute to in vivo viral control and that high HLA allele frequencies may drive the elimination of subdominant yet effective epitopes from circulating viral populations.read more
Citations
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Journal ArticleDOI
Genetic and Immunologic Heterogeneity among Persons Who Control HIV Infection in the Absence of Therapy
Florencia Pereyra,Marylyn M. Addo,Daniel Kaufmann,Yang Liu,Toshiyuki Miura,Almas Rathod,Brett Baker,Alicja Trocha,Alicja Trocha,Rachel Rosenberg,Elizabeth W Mackey,Peggy Ueda,Zhigang Lu,Daniel E. Cohen,Terri Wrin,Christos J. Petropoulos,Eric S. Rosenberg,Bruce D. Walker,Bruce D. Walker +18 more
TL;DR: Even low-level viremia among HIV controllers was associated with measurable T cell dysfunction, which has implications for current prophylactic vaccine strategies.
Journal ArticleDOI
Perforin Expression Directly Ex Vivo by HIV-Specific CD8 + T-Cells Is a Correlate of HIV Elite Control
Adam R. Hersperger,Florencia Pereyra,Martha Nason,Korey Demers,Prameet M. Sheth,Lucy Y. Shin,Colin Kovacs,Benigno Rodriguez,Scott F. Sieg,Leia Teixeira-Johnson,Debbie Gudonis,Paul A. Goepfert,Michael M. Lederman,Ian Frank,George Makedonas,Rupert Kaul,Bruce D. Walker,Bruce D. Walker,Michael R. Betts +18 more
TL;DR: The capability of HIV-specific CD8+ T-cells to rapidly express perforin defines a novel correlate of control in HIV infection.
Journal ArticleDOI
Design and Pre-Clinical Evaluation of a Universal HIV-1 Vaccine
Sven Létourneau,Eung-Jun Im,Tumelo Mashishi,Choechoe Brereton,Anne Bridgeman,Hongbing Yang,Lucy Dorrell,Tao Dong,Bette T. Korber,Bette T. Korber,Andrew J. McMichael,Tomáš Hanke +11 more
TL;DR: This vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape, and has merit in the simplicity of design and delivery.
Design and Pre-Clinical Evaluation of a Universal HIV-1
Eung-Jun Im,Tumelo Mashishi,Choechoe Brereton,Anne Bridgeman,Hongbing Yang,Lucy Dorrell,Tao Dong,Bette T. Korber,Andrew J. McMichael,Tomáš Hanke +9 more
TL;DR: In this article, the authors presented a model for the human immunology unit at the Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, United Kingdom.
Journal ArticleDOI
Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication
Thomas C. Friedrich,Laura E. Valentine,Levi Yant,Eva G. Rakasz,Shari M. Piaskowski,Jessica Furlott,Kimberly L. Weisgrau,Benjamin J. Burwitz,Gemma E. May,Enrique J. León,Taeko Soma,Gnankang Napoé,Saverio Capuano,Nancy A. Wilson,David I. Watkins +14 more
TL;DR: Together, the data suggest that CD8+ T cells targeting a small number of epitopes, along with broad CD4+ T-cell responses, can successfully control the replication of the AIDS virus.
References
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Journal ArticleDOI
SYFPEITHI: database for MHC ligands and peptide motifs.
TL;DR: The first version of the major histocompatibility complex (MHC) databank SYFPEITHI: database for MHC ligands and peptide motifs, is now available to the general public.
Journal ArticleDOI
Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS.
Philip J. R. Goulder,Rodney E. Phillips,Robert A. Colbert,S McAdam,Graham S. Ogg,Martin A. Nowak,P. Giangrande,Graz Luzzi,B. Morgan,Alison J. Edwards,Andrew J. McMichael,Sarah Rowland-Jones +11 more
TL;DR: Six donors who make a strong CTL response to an immunodominant HLA-B27-restricted epitope and two donors who progressed to AIDS, CTL escape to fixation by the same mutation was observed, but only after 9–12 years of epitope stability.
Journal ArticleDOI
Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP)
Michael Bunce,C. M. O'Neill,Martin Barnardo,P. Krausa,M. J. Browning,Peter J. Morris,Kenneth I. Welsh +6 more
TL;DR: The Phototyping set has been used as the sole method of HLA typing for over 1010 individuals and has capacity to detect new alleles, for example, novel amplification patterns suggestive of 4 new HLA-B alleles have been detected.
Journal ArticleDOI
HIV evolution: CTL escape mutation and reversion after transmission.
Alasdair Leslie,Katja Pfafferott,P Chetty,Rika Draenert,Marylyn M. Addo,Margaret E. Feeney,Yanhua Tang,Edward C. Holmes,Todd M. Allen,Julia G. Prado,Marcus Altfeld,Christian Brander,C Dixon,D Ramduth,P M Jeena,S A Thomas,A St John,Timothy Roach,Bernd Kupfer,Graz Luzzi,Adrian Edwards,Graham P. Taylor,Hermione Lyall,Gareth Tudor-Williams,Vas Novelli,Javier Martinez-Picado,Photini Kiepiela,Bruce D. Walker,Philip J. R. Goulder,Philip J. R. Goulder +29 more
TL;DR: Data show that the process of accumulation of escape mutations within HIV is not inevitable, and complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.
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