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Design and validation of HIV peptide pools for detection of HIV-specific CD4+ and CD8+ T cells.

ABSTRACT: Reagents to monitor T cell responses to the entire HIV genome, based on well characterized epitopes, are missing. Evaluation of HIV-specific T cell responses is of importance to study natural infection, and therapeutic and vaccine interventions. Experimentally derived CD4+ and CD8+ HIV epitopes from the HIV molecular immunology database were developed into Class I and Class II HIV megapools (MPs). We assessed HIV responses in persons with HIV pre antiretroviral therapy (ART) (n = 17) and post-ART (n = 18) and compared these responses to 15 controls without HIV (matched by sex at birth, age, and ethnicity). Using the Activation Induced Marker (AIM) assay, we quantified HIV-specific total CD4+, memory CD4+, circulating T follicular helper, total CD8+ and memory CD8+ T cells. We also compared the Class I and Class II HIV MPs to commercially available HIV gag peptide pools. Overall, HIV Class II MP detected HIV-specific CD4+ T cells in 21/35 (60%) HIV positive samples and 0/15 HIV negative samples. HIV Class I MP detected an HIV-specific CD8+ T cells in 17/35 (48.6%) HIV positive samples and 0/15 HIV negative samples. Our innovative HIV MPs are reflective of the entire HIV genome, and its performance is comparable to other commercially available peptide pools. Here, we detected HIV-specific CD4+ and CD8+ T cell responses in people on and off ART, but not in people without HIV.

SUBMITTER: Al-Kolla R

PROVIDER: S-EPMC9380920 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Design and validation of HIV peptide pools for detection of HIV-specific CD4+ and CD8+ T cells.

Al-Kolla Rita R Grifoni Alba A Crotty Shane S Sette Alessandro A Gianella Sara S Dan Jennifer J

PloS one 20220816 8

Reagents to monitor T cell responses to the entire HIV genome, based on well characterized epitopes, are missing. Evaluation of HIV-specific T cell responses is of importance to study natural infection, and therapeutic and vaccine interventions. Experimentally derived CD4+ and CD8+ HIV epitopes from the HIV molecular immunology database were developed into Class I and Class II HIV megapools (MPs). We assessed HIV responses in persons with HIV pre antiretroviral therapy (ART) (n = 17) and post-AR ...[more]

PMID: 35972938

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Project description:UnlabelledCD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection.ImportanceThe ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are important for our understanding of HIV immunopathology.

Dataset Information

Design and validation of HIV peptide pools for detection of HIV-specific CD4+ and CD8+ T cells.

Publications

Design and validation of HIV peptide pools for detection of HIV-specific CD4+ and CD8+ T cells.

Similar Datasets

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