Dendritic cells reveal a broad range of MHC class I epitopes for HIV-1 in persons with suppressed viral load on antiretroviral therapy.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Huang
Xiao-Li
XL
Department of Infectious Diseases and Microbiology, Graduate School of Public Health and School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Fan
Zheng
Z
Borowski
LuAnn
L
Mailliard
Robbie B
RB
Rolland
Morgane
M
Mullins
James I
JI
Day
Richard D
RD
Rinaldo
Charles R
CR
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005805:Genes, MHC Class I; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D018451:Homosexuality, Male; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D019562:Viral Load
D019380:Anti-HIV Agents; D016207:Cytokines; D000939:Epitopes