Frequencies of Ex Vivo-Activated Human Immunodeficiency Virus Type 1-Specific Gamma-Interferon-Producing CD8<sup>+</sup>T Cells in Infected Children Correlate Positively with Plasma Viral Load

Buseyne, Florence; Scott‐Algara, Daniel; Porrot, Françoise; Corre, Béatrice; Bellal, Nassima; Burgard, Marianne; Rouzioux, Christine; Blanche, Stéphane; Rivière, Yves

doi:10.1128/jvi.76.24.12414-12422.2002

Cited by 47 publications

(31 citation statements)

References 77 publications

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“…These observations alone provide strong evidence that MHC class I presentation of Gag epitopes will be essential for the effectiveness of HIV-1 vaccines and concur with the data found from macaque studies. In agreement with other studies (28,29), we have recently shown (30) that there is a positive correlation between total HIV-1-specific CD8 ϩ T cell responses and viral load, but a significant correlation between preferential targeting of Gag by CD8…”

Section: Depletion Of Cd8supporting

confidence: 80%

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Novel and Promiscuous CTL Epitopes in Conserved Regions of Gag Targeted by Individuals with Early Subtype C HIV Type 1 Infection from Southern Africa

Masemola

Mashishi

Khoury

et al. 2004

The Journal of Immunology

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Characterization of optimal CTL epitopes in Gag can provide crucial information for evaluation of candidate vaccines in populations at the epicenter of the HIV-1 epidemic. We screened 38 individuals with recent subtype C HIV-1 infection using overlapping consensus C Gag peptides and hypothesized that unique HLA-restricting alleles in the southern African population would determine novel epitope identity. Seventy-four percent of individuals recognized at least one Gag peptide pool. Ten epitopic regions were identified across p17, p24, and p2p7p1p6, and greater than two-thirds of targeted regions were directed at: TGTEELRSLYNTVATLY (p17, 35%); GPKEPFRDYVDRFFKTLRAEQATQDV (p24, 19%); and RGGKLDKWEKIRLRPGGKKHYMLKHL (p17, 15%). After alignment of these epitopic regions with consensus M and a consensus subtype C sequence from the cohort, it was evident that the regions targeted were highly conserved. Fine epitope mapping revealed that five of nine identified optimal Gag epitopes were novel: HLVWASREL, LVWASRELERF, LYNTVATLY, PFRDYVDRFF, and TLRAEQATQD, and were restricted by unique HLA-Cw*08, HLA-A*30/B*57, HLA-A*29/B*44, and HLA-Cw*03 alleles, respectively. Notably, three of the mapped epitopes were restricted by more than one HLA allele. Although these epitopes were novel and restricted by unique HLA, they overlapped or were embedded within previously described CTL epitopes from subtype B HIV-1 infection. These data emphasize the promiscuous nature of epitope binding and support our hypothesis that HLA diversity between populations can shape fine epitope identity, but may not represent a constraint for universal recognition of Gag in highly conserved domains.

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Section: Depletion Of Cd8supporting

confidence: 80%

“…77 SLYNT VATL 86 (SL-9) and 76 RSLYNTVATLY 86 (RY-11), restricted by HLA-A*0201 and HLA-A*30, respectively (28,29). In our study, we also identified the RY-11 epitope (Fig.…”

Section: Optimal Epitope Recognition and Hla Restrictions In P17mentioning

confidence: 53%

Novel and Promiscuous CTL Epitopes in Conserved Regions of Gag Targeted by Individuals with Early Subtype C HIV Type 1 Infection from Southern Africa

Masemola

Mashishi

Khoury

et al. 2004

The Journal of Immunology

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“…ϩ T-cell responses and viremia in those on combination ART (25,26,29) and greater CTL responses were in children with persistent viremia after treatment (16,27,30). Our findings are similar to the CTL responses found in subjects with both detectable and undetectable viremia except for their finding of the significantly lower response noted in subjects with viral suppression and greater overall magnitude in CTL responses in both groups (16).…”

Section: Discussionsupporting

confidence: 79%

“…The findings in that study were different from ours as previously mentioned. Previous investigators have used recombinant vaccinia vectors expressing single specific viral proteins but not all HIV-1 proteins at once (15,17,(25)(26)(27)(28)30,31) or tetrameric complexes (17,29,30). Most authors have measured IFN-␥ by ELISpot assays, as we did, with the exception of those who used chromium release assays to measure CTL responses (15,17,31).…”

Section: Discussionmentioning

confidence: 99%

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Pediatric HIV-1–Specific Cytotoxic T-Lymphocyte Responses Suggesting Ongoing Viral Replication Despite Combination Antiretroviral Therapy

et al. 2007

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Human immunodeficiency virus-1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses are common in infected adults and usually exhibit rapid decay after combination antiretroviral therapy (ART). CTLs develop later in the first year of life, and the fate of HIV-1-specific responses in perinatally infected children after ART is less well described. HIV-1-specific CTL responses were measured in 17 perinatally infected children and adolescents (ages 3-20 y) receiving combination ART. Seven had prolonged viral suppression (Ͻ400 copies/mL) for 2.5-5.3 y and 10 had persistent viremia (median, 77,550 copies/mL). HIV-1-specific CTL responses were tested by interferon (IFN)-␥ enzyme-linked immunospot (ELISpot) assays using 53 overlapping peptide pools spanning the entire HIV-1 proteome. HIV-1-specific CTL responses were detected in 14 of 17 individuals. Responses to one to four viral proteins were found in eight of 10 individuals with persistent viremia and six of seven with prolonged viral suppression. The magnitude and breadth of CTL responses were similar between groups. HIV-1-specific CTL responses were present in the majority of perinatally infected subjects, irrespective of viremia at evaluation. Because ART-treated infected adults usually have rapid decay of responses, these data suggest viral replication below the limits of detection is more persistent in combination ART-treated perinatally infected pediatric subjects. The long-term clinical implications of these findings remain to be determined. (Pediatr Res 61: 692-697, 2007)

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Cell Lines and Primary Tissues for In‐Vitro Evaluation of Vaccine Efficacy

Meager

2006

Drug Testing in Vitro

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Frequencies of Ex Vivo-Activated Human Immunodeficiency Virus Type 1-Specific Gamma-Interferon-Producing CD8⁺T Cells in Infected Children Correlate Positively with Plasma Viral Load

Abstract: HIV-specific CD8؉ -T-cell subset is dependent upon continuous antigenic stimulation.

Cited by 47 publications

References 77 publications

Novel and Promiscuous CTL Epitopes in Conserved Regions of Gag Targeted by Individuals with Early Subtype C HIV Type 1 Infection from Southern Africa

Novel and Promiscuous CTL Epitopes in Conserved Regions of Gag Targeted by Individuals with Early Subtype C HIV Type 1 Infection from Southern Africa

Pediatric HIV-1–Specific Cytotoxic T-Lymphocyte Responses Suggesting Ongoing Viral Replication Despite Combination Antiretroviral Therapy

Cell Lines and Primary Tissues for In‐Vitro Evaluation of Vaccine Efficacy

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Frequencies of Ex Vivo-Activated Human Immunodeficiency Virus Type 1-Specific Gamma-Interferon-Producing CD8+T Cells in Infected Children Correlate Positively with Plasma Viral Load

Abstract: HIV-specific CD8؉ -T-cell subset is dependent upon continuous antigenic stimulation.

Cited by 47 publications

References 77 publications

Novel and Promiscuous CTL Epitopes in Conserved Regions of Gag Targeted by Individuals with Early Subtype C HIV Type 1 Infection from Southern Africa

Novel and Promiscuous CTL Epitopes in Conserved Regions of Gag Targeted by Individuals with Early Subtype C HIV Type 1 Infection from Southern Africa

Pediatric HIV-1–Specific Cytotoxic T-Lymphocyte Responses Suggesting Ongoing Viral Replication Despite Combination Antiretroviral Therapy

Cell Lines and Primary Tissues for In‐Vitro Evaluation of Vaccine Efficacy

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Frequencies of Ex Vivo-Activated Human Immunodeficiency Virus Type 1-Specific Gamma-Interferon-Producing CD8⁺T Cells in Infected Children Correlate Positively with Plasma Viral Load