Asparagine endopeptidase is not essential for class II MHC antigen presentation but is required for processing of cathepsin L in mice.
Class II MHC molecules survey the endocytic compartments of APCs and present antigenic peptides to CD4 T cells. In this context, lysosomal proteases are essential not only for the generation of antigenic peptides but also for proteolysis of the invariant chain to allow the maturation of class II MHC molecules. Recent studies with protease inhibitors have implicated the asparagine endopeptidase (AEP) in class II MHC-restricted Ag presentation. We now report that AEP-deficient mice show no differences in processing of the invariant chain or maturation of class II MHC products compared with wild-type mice. In the absence of AEP, presentation to primary T cells of OVA and myelin oligodendrocyte glycoprotein, two Ags that contain asparagine residues within or in proximity to the relevant epitopes was unimpaired. Cathepsin (Cat) L, a lysosomal cysteine protease essential for the development to CD4 and NK T cells, fails to be processed into its mature two-chain form in AEP-deficient cells. Despite this, the numbers of CD4 and NK T cells are normal, showing that the single-chain form of Cat L is sufficient for its function in vivo. We conclude that AEP is essential for processing of Cat L but not for class II MHC-restricted Ag presentation.
Maehr
René
R
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Hang
Howard C
HC
Mintern
Justine D
JD
Kim
You-Me
YM
Cuvillier
Armelle
A
Nishimura
Mikio
M
Yamada
Kenji
K
Shirahama-Noda
Kanae
K
Hara-Nishimura
Ikuko
I
Ploegh
Hidde L
HL
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology; D056668:Cathepsin L; D002403:Cathepsins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007527:Isoenzymes / Q000172:deficiency / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology; D000099240:Asparaginyl Endopeptidase
D000944:Antigens, Differentiation, B-Lymphocyte; D056668:Cathepsin L; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D000949:Histocompatibility Antigens Class II; D007527:Isoenzymes; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010047:Ovalbumin; D000099240:Asparaginyl Endopeptidase; C571327:Mog protein, mouse; C045084:invariant chain; C534278:Ctsl protein, mouse