PMID:8612130

Citation	Riese, RJ, Wolf, PR, Brömme, D, Natkin, LR, Villadangos, JA, Ploegh, HL and Chapman, HA (1996) Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading. Immunity 4:357-66
Abstract	Destruction of li by proteolysis is required for MHC class II molecules to bind antigenic peptides, and for transport of the resulting complexes to the cell surface. The cysteine protease cathepsin S is highly expressed in spleen, lymphocytes, monocytes, and other class II-positive cells, and is inducible with interferon-gamma. Specific inhibition of cathepsin S in B lymphoblastoid cells prevented complete proteolysis of li, resulting in accumulation of a class II-associated 13 kDa li fragment in vivo. Consequently, the formation of SDS-stable complexes was markedly reduced. Purified cathepsin S, but not cathepsin B, H, or D, specifically digested li from alpha beta li trimers, generating alpha beta-CLIP complexes capable of binding exogenously added peptide in vitro. Thus, cathepsin S is essential in B cells for effective li proteolysis necessary to render class II molecules competent for binding peptides.
Links	PubMed
Keywords	Antigen Presentation; Antigens, Differentiation, B-Lymphocyte/chemistry; Antigens, Differentiation, B-Lymphocyte/genetics; Antigens, Differentiation, B-Lymphocyte/metabolism; B-Lymphocytes/enzymology; B-Lymphocytes/immunology; Binding Sites; Cathepsins/antagonists & inhibitors; Cathepsins/metabolism; Cell Line; Dipeptides/chemistry; Dipeptides/pharmacology; Histocompatibility Antigens Class II/chemistry; Histocompatibility Antigens Class II/genetics; Histocompatibility Antigens Class II/metabolism; Humans; Protease Inhibitors/chemistry; Protease Inhibitors/pharmacology; Protein Binding; Protein Biosynthesis
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:CATB		GO:0008234: cysteine-type peptidase activity	ECO:0000314:		F		Fig. 1A	complete CACAO 2099
HUMAN:CATB	enables	GO:0008234: cysteine-type peptidase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:CATS		GO:0048002: antigen processing and presentation of peptide antigen	ECO:0000314:		P		Fig. 2, Fig. 5, and Fig. 6	complete CACAO 2117
HUMAN:CATS	enables	GO:0004197: cysteine-type endopeptidase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:CATS		GO:0004197: cysteine-type endopeptidase activity	ECO:0000314:		F		Fig. 2, Fig. 4A, Fig. 5, and Fig. 6	complete CACAO 2088
HUMAN:CATS	involved_in	GO:0048002: antigen processing and presentation of peptide antigen	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CATD		GO:0004190: aspartic-type endopeptidase activity	ECO:0000314:		F		Fig. 7	complete CACAO 2100

References

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