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CTL responses of high functional avidity and broad variant cross-reactivity are associated with HIV control.

Beatriz Mothe | Anuska Llano | Javier Ibarrondo | Jennifer Zamarreño | Mattia Schiaulini | Cristina Miranda | Marta Ruiz-Riol | Christoph T Berger | M José Herrero | Eduard Palou | Montse Plana | Morgane Rolland | Ashok Khatri | David Heckerman | Florencia Pereyra | Bruce D Walker | David Weiner | Roger Paredes | Bonaventura Clotet | Barbara K Felber | George N Pavlakis | James I Mullins | Christian Brander
PloS one | 2012

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.

Pubmed ID: 22238642

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: P01 AI057005
  • Agency: NIAID NIH HHS, United States
    Id: P30 AI060354
  • Agency: Howard Hughes Medical Institute, United States

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This is a list of tools and resources that we have found mentioned in this publication.


HIV Databases (tool)

RRID:SCR_000614

Contains comprehensive data on HIV genetic sequences and immunological epitopes. This collection of databases contains tools to visualize and analyze HIV-related data.

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Sequencher (tool)

RRID:SCR_001528

Software for Next-Generation DNA sequencing, Sanger DNA analysis, and RNA sequencing. It contains sequence analysis tools which include reference-guided alignments, de novo assembly, variant calling, and SNP analyses. It has integrated the Cufflinks suite for in-depth transcript analysis and differential gene expression of RNA-Seq data.

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