Processing and presentation of exogenous HLA class I peptides by dendritic cells from human immunodeficiency virus type 1-infected persons

J Virol. 2005 Mar;79(5):3052-62. doi: 10.1128/JVI.79.5.3052-3062.2005.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen Presentation / drug effects
  • Antimetabolites / pharmacology
  • CD8-Positive T-Lymphocytes / immunology
  • Case-Control Studies
  • Dendritic Cells / immunology*
  • HIV Infections / immunology*
  • HIV-1
  • HLA Antigens / metabolism*
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • In Vitro Techniques
  • Oligopeptides / immunology

Substances

  • Antimetabolites
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Oligopeptides