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The role of phagosomal pH on the size-dependent efficiency of cross-presentation by dendritic cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
9182 619 2009 7 PDF Available
Title
The role of phagosomal pH on the size-dependent efficiency of cross-presentation by dendritic cells
Abstract

Vaccines able to stimulate CD8+ T cells are crucial in controlling a broad range of infectious diseases and tumors. To induce effective CD8+ T cell responses, exogenous antigen has to be cross-presented onto major histocompatibility complex (MHC) class I molecules by dendritic cells. Although particle size has been recognized as a critical factor of vaccine design, it is unclear how the size of vaccine carriers impacts the intracellular processing of exogenous antigen and cross-presentation onto MHC class I molecules. In this study, by using polystyrene beads with narrowly defined sizes as model antigen carriers, we demonstrate that particle size mediates the efficiency of cross-presentation of exogenous antigens. By examining the intracellular trafficking, kinetics of phagosomal pH and degradation of antigens bounded to beads, we illustrate the possible mechanisms attributed to the profound effect of particle size on the efficiency of cross-presentation. Antigen bounded to 50 nm beads was shuttled rapidly to an acidic environment within half an hour post-exposure to cells, leading to its rapid and unregulated degradation and inefficient cross-presentation. In contrast, antigen bounded to 500 nm and 3 μm beads remained in a more neutral environment, which preserved the majority of antigens, leaving it available for the generation of peptides to be loaded onto MHC class I molecules. We conclude that the size of antigen carriers plays a critical role in directing antigen to the class I antigen presentation pathway. Our results, together with previous in vivo studies on the effect of particle size on CD8+ T cell responses, provide insight into the rational design of vaccines for the stimulation of cell-mediated immunity.

Keywords
Nanoparticles; Vaccine; Antigen presentation; Dendritic cells; Phagosomal pH
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The role of phagosomal pH on the size-dependent efficiency of cross-presentation by dendritic cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 7, March 2009, Pages 1356–1362
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us