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Curr Opin Immunol. 2014 Feb;26:63-8. doi: 10.1016/j.coi.2013.11.001. Epub 2013 Nov 30.

The ins-and-outs of endosomal antigens for cross-presentation.

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Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany. Electronic address:


The efficiency of antigen cross-presentation, which is the presentation of extracellular antigens on MHC I molecules, critically depends on the stability of the internalized antigens. Since rapid degradation within the lysosomal compartment impairs cross-presentation, potent cross-presenting cells display several mechanisms to prevent activation of lysosomal proteases. Additionally, distinct endocytic receptors can target internalized antigens towards non-degradative early endosomes, from where efficient cross-presentation can occur. From these endosomes, antigens need to be processed for loading on MHC I molecules, which can occur by endo/lysosomal proteases or after translocation into the cytosol by the proteasome. Although the underlying mechanisms require further investigations, increasing evidence points out a decisive role of the ER-associated degradation machinery in such antigen translocation.

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