title: CTL responses of high functional avidity and broad variant cross-reactivity are associated with HIV control.
abstract: Cytotoxic T lymphocyte (CTL) responses targeting specific HIV proteins, in particular Gag, have been associated with relative control of viral replication in vivo. However, Gag-specific CTL can also be detected in individuals who do not control the virus and it remains thus unclear how Gag-specific CTL may mediate the beneficial effects in some individuals but not in others. Here, we used a 10mer peptide set spanning HIV Gag-p24 to determine immunogen-specific T-cell responses and to assess functional properties including functional avidity and cross-reactivity in 25 HIV-1 controllers and 25 non-controllers without protective HLA class I alleles. Our data challenge the common belief that Gag-specific T cell responses dominate the virus-specific immunity exclusively in HIV-1 controllers as both groups mounted responses of comparable breadths and magnitudes against the p24 sequence. However, responses in controllers reacted to lower antigen concentrations and recognized more epitope variants than responses in non-controllers. These cross-sectional data, largely independent of particular HLA genetics and generated using direct ex-vivo samples thus identify T cell responses of high functional avidity and with broad variant reactivity as potential functional immune correlates of relative HIV control.
authors.affiliation: IrsiCaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mothe
authors.forename: Anuska
authors.initials: A
authors.lastname: Llano
authors.forename: Javier
authors.initials: J
authors.lastname: Ibarrondo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zamarreño
authors.forename: Mattia
authors.initials: M
authors.lastname: Schiaulini
authors.forename: Cristina
authors.initials: C
authors.lastname: Miranda
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Riol
authors.forename: Christoph T
authors.initials: CT
authors.lastname: Berger
authors.forename: M José
authors.initials: MJ
authors.lastname: Herrero
authors.forename: Eduard
authors.initials: E
authors.lastname: Palou
authors.forename: Montse
authors.initials: M
authors.lastname: Plana
authors.forename: Morgane
authors.initials: M
authors.lastname: Rolland
authors.forename: Ashok
authors.initials: A
authors.lastname: Khatri
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: David
authors.initials: D
authors.lastname: Weiner
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D003429:Cross Reactions / Q000276:immunology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D055815:Young Adult