Dendritic cells reveal a broad range of MHC class I epitopes for HIV-1 in persons with suppressed viral load on antiretroviral therapy |
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Authors: | Huang Xiao-Li Fan Zheng Borowski LuAnn Mailliard Robbie B Rolland Morgane Mullins James I Day Richard D Rinaldo Charles R |
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Institution: | Department of Infectious Diseases and Microbiology, Graduate School of Public Health and School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America. |
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Abstract: | BackgroundHIV-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.Principal FindingsWe 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.SignificanceThere 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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