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

Ellen Leitman (1, 2) , Christine Palmer (3) , Søren Buus (4) , Fabian Chen (5) , Lynn Riddell (6) , Stuart Sims (7) , Paul Klenerman (8, 1) , Asier Saez-Cirion (9) , Bruce Walker (2, 10) , Paul Hess (11) , Marcus Altfeld (2) , Philippa Matthews (1, 6, 8) , Philip Goulder (1, 10)

1 University of Oxford
2 HMS - Harvard Medical School [Boston]
3 Ragon Institute of MGH, MIT and Harvard
4 UCPH - University of Copenhagen = Københavns Universitet
5 Royal Berkshire Hospital
6 NHS Foundation Trust [London]
7 UZH - Universität Zürich [Zürich] = University of Zurich
8 John Radcliffe Hospital [Oxford University Hospital]
9 HIV, Inflammation et persistance - HIV, Inflammation and Persistence
10 UKZN - University of KwaZulu-Natal [Durban, Afrique du Sud]
11 NC State - North Carolina State University [Raleigh]

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.

Domains: Life Sciences [q-bio]; Immunology

Ellen Leitman, Christine Palmer, Søren Buus, Fabian Chen, Lynn Riddell, et al.. Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificities. PLoS ONE, 2017, 12 (10), pp.e0184496. ⟨10.1371/journal.pone.0184496⟩. ⟨pasteur-02549950⟩