Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes.
Major histocompatibility complex (MHC) class II molecules present products of lysosomal proteolysis to CD4(+) T cells. Although extracellular antigen uptake is considered to be the main source of MHC class II ligands, a few intracellular antigens have been described to gain access to MHC class II loading after macroautophagy. However, the general relevance and efficacy of this pathway is unknown. Here we demonstrated constitutive autophagosome formation in MHC class II-positive cells, including dendritic, B, and epithelial cells. The autophagosomes continuously fuse with multivesicular MHC class II-loading compartments. This pathway was of functional relevance, because targeting of the influenza matrix protein 1 to autophagosomes via fusion to the autophagosome-associated protein Atg8/LC3 led to strongly enhanced MHC class II presentation to CD4(+) T cell clones. We suggest that macroautophagy constitutively and efficiently delivers cytosolic proteins for MHC class II presentation and can be harnessed for improved helper T cell stimulation.
Schmid
Dorothee
D
Laboratory of Viral Immunobiology and Christopher H Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021, USA.
Pypaert
Marc
M
Münz
Christian
C
D017951:Antigen Presentation / Q000276:immunology*; D001343:Autophagy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D010588:Phagosomes / Q000276:immunology* / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000949:Histocompatibility Antigens Class II; D034741:RNA, Small Interfering