Endogenous MHC class II processing of a viral nuclear antigen after autophagy.
CD4+ T cells classically recognize antigens that are endocytosed and processed in lysosomes for presentation on major histocompatibility complex (MHC) class II molecules. Here, endogenous Epstein-Barr virus nuclear antigen 1 (EBNA1) was found to gain access to this pathway by autophagy. On inhibition of lysosomal acidification, EBNA1, the dominant CD4+ T cell antigen of latent Epstein-Barr virus infection, slowly accumulated in cytosolic autophagosomes. In addition, inhibition of autophagy decreased recognition by EBNA1-specific CD4+ T cell clones. Thus, lysosomal processing after autophagy may contribute to MHC class II-restricted surveillance of long-lived endogenous antigens including nuclear proteins relevant to disease.
Paludan
Casper
C
Laboratory of Viral Immunobiology, Rockefeller University, New York, NY 10021, USA.
Schmid
Dorothee
D
Landthaler
Markus
M
Vockerodt
Martina
M
Kube
Dieter
D
Tuschl
Thomas
T
Münz
Christian
C
D000818:Animals; D017951:Antigen Presentation; D001343:Autophagy; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014162:Transfection
D019309:Epstein-Barr Virus Nuclear Antigens; D000949:Histocompatibility Antigens Class II; D002738:Chloroquine; D046988:Proteasome Endopeptidase Complex; C417029:EBV-encoded nuclear antigen 1