Major histocompatibility complex class II-restricted presentation of a cytosolic antigen by autophagy.
Biochemical and functional studies have demonstrated major histocompatibility complex (MHC) class II-restricted presentation of peptides derived from cytosolic proteins, but the underlying processing and presentation pathways have remained elusive. Here we show that endogenous presentation of an epitope derived from the cytosolic protein neomycin phosphotransferase II (NeoR) on MHC class II is mediated by autophagy. This presentation pathway involves the sequestration of NeoR into autophagosomes, and subsequent delivery into the lytic compartment. These results identify endosomes/lysosomes as the processing compartment for cytosolic antigens and furthermore link endogenous antigen presentation on MHC class II with the process of cellular protein turnover by autophagy.
Klinische Kooperationsgruppe, GSF-Institut für Klinische Molekularbiologie, Munich, Germany.
Falk
F
Nimmerjahn
Slavoljub
S
Milosevic
Uta
U
Behrends
Elizabeth M
EM
Jaffee
Drew M
DM
Pardoll
Georg W
GW
Bornkamm
Josef
J
Mautner
D017951:Antigen Presentation; D001343:Autophagy; D002460:Cell Line; D003600:Cytosol / Q000276:immunology*; D006682:HLA-DP Antigens / Q000502:physiology; D059868:HLA-DP beta-Chains; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006801:Humans; D019868:Kanamycin Kinase / Q000032:analysis / Q000276:immunology*; D008247:Lysosomes / Q000737:chemistry / Q000378:metabolism; D014617:Vacuoles / Q000201:enzymology
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C055961:HLA-DPw3 antigen; D000949:Histocompatibility Antigens Class II; D019868:Kanamycin Kinase