title: Asparagine endopeptidase can initiate the removal of the MHC class II invariant chain chaperone.
abstract: The invariant chain (Ii) chaperone for MHC class II molecules is crucial for their effective function. Equally important is its removal. Cathepsins S or L are known to be required for the final stages of Ii removal in different APCs, but the enzymes which initiate Ii processing have not been identified. Here we show that this step can be performed in B lymphocytes by asparagine endopeptidase (AEP), which targets different asparagine residues in the lumenal domain of human and mouse invariant chain. Inhibition of AEP activity slows invariant chain processing and hinders the expression of an antigenic peptide engineered to replace the groove binding region of Ii (CLIP). However, the initiation of Ii removal can also be performed by other proteases, reflecting the importance of this step.
authors.affiliation: Division of Cell Biology and Immunology, School of Life Sciences, University of Dundee, Dow Street, United Kingdom. b.manoury@dundee.ac.uk
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Manoury
authors.forename: Daniela
authors.initials: D
authors.lastname: Mazzeo
authors.forename: Dongtao Ni
authors.initials: DN
authors.lastname: Li
authors.forename: Jeremy
authors.initials: J
authors.lastname: Billson
authors.forename: Kylie
authors.initials: K
authors.lastname: Loak
authors.forename: Philippe
authors.initials: P
authors.lastname: Benaroch
authors.forename: Colin
authors.initials: C
authors.lastname: Watts
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000502:physiology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D051379:Mice
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; D003546:Cysteine Endopeptidases; C447421:asparaginyl endopeptidase, lysosomal