title: Alternative effector-function profiling identifies broad HIV-specific T-cell responses in highly HIV-exposed individuals who remain uninfected.
abstract: 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.
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona.
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Riol
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona.
authors.forename: Anuska
authors.initials: A
authors.lastname: Llano
authors.affiliation: Center for HIV Prevention Research, University of California-Los Angeles.
authors.forename: Javier
authors.initials: J
authors.lastname: Ibarrondo
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zamarreño
authors.affiliation: Los Alamos National Laboratory, New Mexico.
authors.forename: Karina
authors.initials: K
authors.lastname: Yusim
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bach
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona Fundació Lluita Contra La Sida, Hospital Universitari Germans Trias i Pujol University of Vic, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mothe
authors.affiliation: Biokit Research and Development, Lliçà d'Amunt.
authors.forename: Susana
authors.initials: S
authors.lastname: Perez-Alvarez
authors.affiliation: Flow Cytometry Facility, Health Sciences Research Institute Germans Trias i Pujol, Badalona.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Fernandez
authors.affiliation: Flow Cytometry Facility, Health Sciences Research Institute Germans Trias i Pujol, Badalona.
authors.forename: Gerard
authors.initials: G
authors.lastname: Requena
authors.affiliation: BCN Checkpoint, Projecte dels NOMS-Hispanosida.
authors.forename: Michael
authors.initials: M
authors.lastname: Meulbroek
authors.affiliation: BCN Checkpoint, Projecte dels NOMS-Hispanosida.
authors.forename: Ferran
authors.initials: F
authors.lastname: Pujol
authors.affiliation: HIVACAT, Hospital Clinic-Fundació Clinic.
authors.forename: Agathe
authors.initials: A
authors.lastname: Leon
authors.affiliation: Fundació Lluita Contra La Sida, Hospital Universitari Germans Trias i Pujol.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cobarsi
authors.affiliation: Los Alamos National Laboratory, New Mexico.
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona Fundació Lluita Contra La Sida, Hospital Universitari Germans Trias i Pujol University of Vic, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.affiliation: Asociacion Civil Impacta Salud y Educacion, Lima, Peru.
authors.forename: Carmela
authors.initials: C
authors.lastname: Ganoza
authors.affiliation: Asociacion Civil Impacta Salud y Educacion, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona Fundació Lluita Contra La Sida, Hospital Universitari Germans Trias i Pujol.
authors.forename: Josep
authors.initials: J
authors.lastname: Coll
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona Institució Catalana de Recerca i Estudis Avancats (ICREA), Barcelona University of Vic, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D060467:Disease Resistance; D006678:HIV / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D016207:Cytokines
keywords: HIV infection; T-cell responses; Th1 cytokines; Th17 cytokines; Th2 cytokines; boosted flow cytometry; highly exposed seronegative; toggled peptides