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

Ellen M. Leitman; Christine D. Palmer; Søren Buus; Fabian Chen; Lynn Riddell; Stuart Sims; Paul Klenerman; Asier Sáez-Cirión; Bruce D. Walker; Paul R. Hess; Marcus Altfeld; Philippa C. Matthews; Philip J.R. Goulder

doi:10.1371/journal.pone.0184496

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

Ellen M. Leitman, Christine D. Palmer, Søren Buus, Fabian Chen, Lynn Riddell, Stuart Sims, Paul Klenerman, Asier Sáez-Cirión, Bruce D. Walker, Paul R. Hess, Marcus Altfeld, Philippa C. Matthews, Philip J.R. Goulder^*

^*Corresponding author for this work

2 Citations (Scopus)

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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.

Original language	English
Article number	e0184496
Journal	PLOS ONE
Volume	12
Issue number	10
Number of pages	13
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0184496
Publication status	Published - Oct 2017

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Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificitiesFinal published version, 3.5 MBLicence: CC BY

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title = "Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificities",

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.",

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year = "2017",

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doi = "10.1371/journal.pone.0184496",

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T1 - Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificities

AU - Leitman, Ellen M.

AU - Palmer, Christine D.

AU - Buus, Søren

AU - Chen, Fabian

AU - Riddell, Lynn

AU - Sims, Stuart

AU - Klenerman, Paul

AU - Sáez-Cirión, Asier

AU - Walker, Bruce D.

AU - Hess, Paul R.

AU - Altfeld, Marcus

AU - Matthews, Philippa C.

AU - Goulder, Philip J.R.

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0184496

DO - 10.1371/journal.pone.0184496

M3 - Review

C2 - 29020090

AN - SCOPUS:85031110990

SN - 1932-6203

VL - 12

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 10

M1 - e0184496

ER -

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

Abstract

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