Essential role for cholesterol in the delivery of exogenous antigens to the MHC class I-presentation pathway.
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.
Albrecht
Imke
I
Biozentrum, University of Basel, Klingelbergstrasse 50, CH 4056 Basel, Switzerland.
Gatfield
John
J
Mini
Thierry
T
Jeno
Paul
P
Pieters
Jean
J
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D019308:Palmitic Acid / Q000378:metabolism; D010873:Pinocytosis / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D019308:Palmitic Acid; D010047:Ovalbumin; D002784:Cholesterol