Alternative effector-function profiling identifies broad HIV-specific T-cell responses in highly HIV-exposed individuals who remain uninfected

Marta Ruiz-Riol, Anuska Llano, Javier Ibarrondo, Jennifer Zamarreño, Karina Yusim, Vanessa Bach, Beatriz Mothe, Susana Perez-Alvarez, Marco A. Fernandez, Gerard Requena, Michael Meulbroek, Ferran Pujol, Agathe Leon, Patricia Cobarsi, Bette T. Korber, Bonaventura Clotet, Carmela Ganoza, Jorge Sanchez, Josep Coll, Christian Brander

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12 Citations (Scopus)


© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine-like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders.
Original languageEnglish
Pages (from-to)936-946
JournalJournal of Infectious Diseases
Issue number6
Publication statusPublished - 1 Jan 2015


  • boosted flow cytometry
  • highly exposed seronegative
  • HIV infection
  • T-cell responses
  • Th1 cytokines
  • Th17 cytokines
  • Th2 cytokines
  • toggled peptides


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