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PLoS One. 2017 Oct 11;12(10):e0184496. doi: 10.1371/journal.pone.0184496. eCollection 2017.

Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificities.

Author information

1
Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
2
Harvard Medical School, Boston, Massachusetts, United States of America.
3
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
4
Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
5
Department of Sexual Health, Royal Berkshire Hospital, Reading, United Kingdom.
6
Integrated Sexual Health Services, Northamptonshire Healthcare NHS Trust, Northampton, United Kingdom.
7
Institute of Virology, University of Zurich, Zurich, Switzerland.
8
NIHR Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
9
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
10
Institut Pasteur, Unité HIV, Inflammation et Persistance, Paris, France.
11
HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
12
Immunology Program, Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, United States of America.
13
Virus Immunology Unit, Heinrich-Pette-Institut, Hamburg, Germany.
14
Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom.

Abstract

Antigen-specific T-cells are highly variable, spanning potent antiviral efficacy and damaging auto-reactivity. In virus infections, identifying the most efficacious responses is critical to vaccine design. However, current methods depend on indirect measures or on ex vivo expanded CTL clones. We here describe a novel application of cytotoxic saporin-conjugated tetramers to kill antigen-specific T-cells without significant off-target effects. The relative efficacy of distinct antiviral CD8+ T-cell specificity can be directly assessed via antigen-specific CD8+ T-cell depletion. The utility of these reagents is demonstrated here in identifying the CD8+ T-cell specificity most effective in preventing HIV progression in HIV-infected HLA-B*27-positive immune controllers.

PMID:
29020090
PMCID:
PMC5636067
DOI:
10.1371/journal.pone.0184496
[Indexed for MEDLINE]
Free PMC Article

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