Two new proteases in the MHC class I processing pathway.
The proteasome generates exact major histocompatibility complex (MHC) class I ligands as well as NH2-terminal-extended precursor peptides. The proteases responsible for the final NH2-terminal trimming of the precursor peptides had, until now, not been determined. By using specific selective criteria we purified two cytosolic proteolytic activities, puromycin-sensitive aminopeptidase and bleomycin hydrolase. These proteases could remove NH2-terminal amino acids from the vesicular stomatitis virus nucleoprotein cytotoxic T cell epitope 52-59 (RGYVYQGL) resulting, in combination with proteasomes, in the generation of the correct epitope. Our data provide evidence for the existence of redundant systems acting downstream of the proteasome in the antigen-processing pathway for MHC class I molecules.
Stoltze
L
L
Institute for Cell Biology, Department of Immunology, University of Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany.
Schirle
M
M
Schwarz
G
G
Schröter
C
C
Thompson
M W
MW
Hersh
L B
LB
Kalbacher
H
H
Stevanovic
S
S
Rammensee
H G
HG
Schild
H
H
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism; D010450:Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D019251:Nucleocapsid / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019590:Nucleocapsid Proteins; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology
D000590:Amino Acid Chloromethyl Ketones; D000956:Antigens, Viral; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009097:Multienzyme Complexes; D019590:Nucleocapsid Proteins; C055604:alanyl-alanyl-phenylalanine chloromethyl ketone; D010450:Endopeptidases; D000626:Aminopeptidases; C025579:enkephalin degrading enzyme; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase; D046988:Proteasome Endopeptidase Complex