Dendritic Cells Reveal a Broad Range of MHC Class I Epitopes for HIV-1 in Persons with Suppressed Viral Load on Antiretroviral Therapy

Department of Infectious Diseases and Microbiology, Graduate School of Public Health and School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
PLoS ONE (Impact Factor: 3.23). 09/2010; 5(9):e12936. DOI: 10.1371/journal.pone.0012936
Source: PubMed


HIV-1 remains sequestered during antiretroviral therapy (ART) and can resume high-level replication upon cessation of ART or development of drug resistance. Reactivity of memory CD8(+) T lymphocytes to HIV-1 could potentially inhibit this residual viral replication, but is largely muted by ART in relation to suppression of viral antigen burden. Dendritic cells (DC) are important for MHC class I processing and presentation of peptide epitopes to memory CD8(+) T cells, and could potentially be targeted to activate memory CD8(+) T cells to a broad array of HIV-1 epitopes during ART.
We show for the first time that HIV-1 peptide-loaded, CD40L-matured DC from HIV-1 infected persons on ART induce IFN gamma production by CD8(+) T cells specific for a much broader range and magnitude of Gag and Nef epitopes than do peptides without DC. The DC also reveal novel, MHC class I restricted, Gag and Nef epitopes that are able to induce polyfunctional T cells producing various combinations of IFN gamma, interleukin 2, tumor necrosis factor alpha, macrophage inhibitory protein 1 beta and the cytotoxic de-granulation molecule CD107a.
There is an underlying, broad antigenic spectrum of anti-HIV-1, memory CD8(+) T cell reactivity in persons on ART that is revealed by DC. This supports the use of DC-based immunotherapy for HIV-1 infection.

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Available from: James I Mullins, Jul 18, 2014
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    • "When VDRFYKTLRAQASQ peptide was added exogenously to DCs in vitro its presentation required intracellular processing (Figure 3C and 6B), suggesting an active role of DCs in generating MHC II-bound peptides from an exogenous peptide source [23], [37] and not a direct binding of peptides to HLA molecules at the cell surface [22], [38]. Three out of the four HIV gag p24 mimetopes, added exogenously, were not detected by LC-MS/MS (Figure S1) and did not elicit proliferation of CD4+ T cells measured by a CFSE dilution assay (Figure S6). "
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    Preview · Article · Jul 2012 · PLoS ONE
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    • "This is similar to optimal activation of anti-EBV CTL by peptide-loaded DC (Wheatley et al., 1998; Redchenko and Rickinson, 1999; Subklewe et al., 1999a,b, 2001, 2005; Lin et al., 2002). Other studies have revealed polyfunctional CD8 + and CD4 + T cell reactivity and new MHC class I epitopes for HIV-1 Gag and Nef using peptideloaded DC (Huang et al., 2010). Importantly, we have used this DC model to map epitopes of HHV-8 lytic and latency proteins with libraries of synthetic, 15mer peptides overlapping by 11aa (Lepone et al., 2010). "
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