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International Immunology Advance Access published online on April 11, 2006
International Immunology, doi:10.1093/intimm/dxl013
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received May 15, 2005
Accepted February 17, 2006

Article

Essential role for cholesterol in the delivery of exogenous antigens to the MHC class I-presentation pathway

Imke Albrecht 1, John Gatfield 1, Thierry Mini 1, Paul Jeno 1, and Jean Pieters 1 *

1 Biozentrum, University of Basel, Klingelbergstrasse 50, CH 4056 Basel, Switzerland

* To whom correspondence should be addressed.
Jean Pieters, E-mail: jean.pieters{at}unibas.ch


  Abstract

Cross-presentation, which is crucial for the generation of immunity against virus-infected and tumor cells, requires exogenous antigens to be internalized into antigen-presenting cells (APCs) followed by translocation to the cytosol by unknown mechanisms. One important entry route for such antigens is macropinocytosis. We here describe that cholesterol is essential for cross-presentation of antigens loaded via macropinocytosis into APCs. Modification of antigens by palmitoylation to target antigens to cholesterol-enriched plasma membrane domains resulted in a dramatically increased T cell activation. These results define cholesterol as an essential factor for cross-presentation and suggest that specific modification of antigens to increase their affinity for cholesterol may be utilized to enhance immunity.

Keywords: macropinocytosis; cholesterol; antigen presentation.
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