Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input fromautophagosomes

Immunity 2007 26:79-92

Speaker: 徐英展                            Time: 200/03/28 15:10~16:00

Commentator: 謝奇璋 老師                   Place: Room 601

Abstract:

CD4⁺ T cells are key contributor of adaptive immunity, and the CD4⁺ T cell priming is triggered by major histocompatibility complex (MHC) molecules-antigen peptide complexes of antigen–presenting cells (APCs). Although exogenous antigens interacting with HLA-DM/MHC class II antigen loading complexes in MHC class II compartments (MIICs) are the main source for MHC class II-mediated antigen presenting pathway, some cytosolic or nuclear proteins also presented onto MHC class II molecules. The role of macroautophagy, a self-recycling pathway which can deliver cytosolic materials into the endosome / lysosome after induction, has been implicated^{2, 3}. In this study, the authors use GFP-LC3 transfectants and chloroquine (CQ) to inhibit lysosomalacidification to evaluate the efficiency of macroautophagy for endogenous MHC class II antigen processing. They found that macroautophagy was a constitutively active pathway in human epithelial cell lines and dendritic cells, and autophagosomes continuously fuse with MIICs in these cells. Targeting to autophagosome by fusion the antigen to LC3 would enhance themacroautophagic degradation, MHC class II presenting and thus CD4⁺ T cells recognition. In conclusion, macroautophagy constitutively and efficiently delivers cytosolic antigens for endogenous MHC class II antigen presentation.

References:

1. Busch, R. et al. Accessory molecules for MHC class II peptide loading. Curr. Opin. Immunol. 2000, 12:99-106

2. Paludan, C. et al. Endogenous MHC class II processing of a viral nuclear antigen  after autophagy. Science 2005, 307:593-596

3. Schmid, D., and Müz, C. Immune surveillance of intracellular pathogens via autophagy. Cell Death Differ. 2005, 12 (suppl 2):1519-1527