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Journal of Virology, March 2005, p. 3052-3062, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3052-3062.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Processing and Presentation of Exogenous HLA Class I Peptides by Dendritic Cells from Human Immunodeficiency Virus Type 1-Infected Persons

Xiao-Li Huang,1 Zheng Fan,1 Bonnie A. Colleton,1 Rico Buchli,2 Hongyi Li,1 William H. Hildebrand,2 and Charles R. Rinaldo Jr.1,3*

Departments of Infectious Diseases and Microbiology,1 Pathology, Graduate School of Public Health and School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania,3 University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma2

Received 7 August 2004/ Accepted 7 October 2004

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.

* Corresponding author. Mailing address: 419C Crabtree Hall, University of Pittsburgh Graduate School of Public Health, 130 DeSoto St., Pittsburgh, PA 15261. Phone: (412) 624-3928. Fax: (412) 624-4953. E-mail: rinaldo{at}pitt.edu.

Journal of Virology, March 2005, p. 3052-3062, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3052-3062.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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