2012
DOI: 10.1371/journal.pone.0029717
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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 properti… Show more

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Cited by 122 publications
(145 citation statements)
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“…The CE selection included analysis of MHC binding prediction to address immunogenicity in humans, and we found that epitopes from all MHC class I known supertypes were represented in Gag CE. As reported previously, 19 in a group of 50 people, >30 epitopes were recognized using >40 HLA alleles. No similar laboratory studies have been performed for Env, but in silico analysis indicated that the Env CE together represent a predicted 141 MHC Class I and 760 MHC Class II epitopes with an IC50 value < 50 nmol (www.iedb.org).…”
Section: Resultssupporting
confidence: 75%
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“…The CE selection included analysis of MHC binding prediction to address immunogenicity in humans, and we found that epitopes from all MHC class I known supertypes were represented in Gag CE. As reported previously, 19 in a group of 50 people, >30 epitopes were recognized using >40 HLA alleles. No similar laboratory studies have been performed for Env, but in silico analysis indicated that the Env CE together represent a predicted 141 MHC Class I and 760 MHC Class II epitopes with an IC50 value < 50 nmol (www.iedb.org).…”
Section: Resultssupporting
confidence: 75%
“…During primary infection in humans the reduction of the original viral burst is associated with the emergence of HIV-specific cytotoxic CD8 + T lymphocytes (CTL). 19 , 33 , 34 , 3953 Their role in controlling viremia was confirmed by systemic CD8 depletion in SIV/SHIV infected macaques, which resulted in a rapid increase in viremia, 5457 demonstrating a CD8-dependent immunological mechanisms of viral control. 5867 Failure to contain viral replication in macaques correlated with the emergence of viral mutants that escaped from CTL immune surveillance.…”
Section: Introductionmentioning
confidence: 89%
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“…To address the problem of viral variability, many approaches have been tested including strategies that use consensus, center-of-tree or ancestral sequences, multiple strains or mosaic immunogens, immunogens consisting of known epitopes, and chimeric molecules expressing a selection of the most conserved epitopes from different clades of HIV . In our approach (20)(21)(22), we designed a plasmid DNA (pDNA) vaccine to focus the immune response to conserved elements (CE) of the HIV-1 proteome based on stringent conservation, broad HLA-coverage, and association with HIV control (19,(23)(24)(25). The p24…”
mentioning
confidence: 99%