Processing and presentation of exogenous HLA class I peptides by dendritic cells from human immunodeficiency virus type 1-infected persons.
Dendritic cells (DCs) loaded with viral peptides are a potential form of immunotherapy of human immunodeficiency virus type 1 (HIV-1) infection. We show that DCs derived from blood monocytes of subjects with chronic HIV-1 infection on combination antiretroviral drug therapy have increases in expression of HLA, T-cell coreceptor, and T-cell activation molecules in response to the DC maturation factor CD40L comparable to those from uninfected persons. Mature DCs (mDCs) loaded with HLA A*0201-restricted viral peptides of the optimal length (9-mer) were more efficient at activating antiviral CD8(+) T cells than were immature DCs or peptide alone. Optimal presentation of these exogenous peptides required uptake and vesicular trafficking and was comparable in DCs derived from HIV-1-infected and uninfected persons. Furthermore, DCs from HIV-1-infected and uninfected persons had similar capacities to process viral peptides with C-terminal and N-terminal extensions through their proteasomal and cytosolic pathways, respectively. We conclude that DCs derived from HIV-1-infected persons have similar abilities to process exogenous peptides for presentation to CD8(+) T cells as those from uninfected persons. This conclusion supports the use of DCs loaded with synthetic peptides in immunotherapy of HIV-1 infection.
Huang
Xiao-Li
XL
University of Pittsburgh Graduate School of Public Health, 130 DeSoto St., Pittsburgh, PA 15261, USA.
Fan
Zheng
Z
Colleton
Bonnie A
BA
Buchli
Rico
R
Li
Hongyi
H
Hildebrand
William H
WH
Rinaldo
Charles R
CR
D017951:Antigen Presentation / Q000187:drug effects; D000963:Antimetabolites / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006680:HLA Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000276:immunology
D000963:Antimetabolites; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D009842:Oligopeptides