Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
Curr Opin Immunol. 2014 Feb;26:63-8. doi: 10.1016/j.coi.2013.11.001. Epub 2013 Nov 30.
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.
抗原交叉呈递的效率，即细胞外抗原在 MHC I 分子上的呈递，严重依赖于内化抗原的稳定性。由于溶酶体腔内的快速降解会损害交叉呈递，因此有效的交叉呈递细胞会显示出几种机制来防止溶酶体蛋白酶的激活。此外，不同的内吞受体可以将内化的抗原靶向非降解性的早期内体，从而有效地进行交叉呈递。从这些内体中，抗原需要进行加工才能加载到 MHC I 分子上，这可以通过内体/溶酶体蛋白酶完成，或者通过蛋白酶体转运到细胞质中完成。尽管潜在的机制需要进一步研究，但越来越多的证据表明 ER 相关降解机制在这种抗原转运中起着决定性的作用。
