title: Cathepsin V is involved in the degradation of invariant chain in human thymus and is overexpressed in myasthenia gravis.
abstract: Stepwise degradation of the invariant chain (Ii) is required for the binding of antigenic peptides to MHC class II molecules. Cathepsin (Cat) L in the murine thymus and Cat S in peripheral APCs have both been implicated in the last step of Ii degradation that gives rise to the class II-associated invariant chain peptides (CLIP). Cat V has been recently described as highly homologous to Cat L and exclusively expressed in human thymus and testis, but with no mouse orthologue. We report that Cat V is the dominant cysteine protease in cortical human thymic epithelial cells, while Cat L and Cat S seem to be restricted to dendritic and macrophage-like cells. Active Cat V in thymic lysosomal preparations was demonstrated by active-site labeling. Recombinant Cat V was capable of converting Ii into CLIP efficiently, suggesting that Cat V is the protease that controls the generation of alphabeta-CLIP complexes in the human thymus, in analogy to Cat L in mouse. Comparison of Cat V expression between thymi from patients with myasthenia gravis and healthy controls revealed a significantly higher expression level in the pathological samples, suggesting a potential involvement of this protease in the immunopathogenesis of myasthenia gravis, an autoimmune disease almost invariably associated with thymic pathology.
authors.affiliation: Neuroimmunology, Department of Neurology, Tübingen University Hospital, Auf der Morgenstelle 15, 72076 Tübingen, Germany. eva.tolosa@uni-tuebingen.de
authors.forename: Eva
authors.initials: E
authors.lastname: Tolosa
authors.forename: Weijie
authors.initials: W
authors.lastname: Li
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wienhold
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Denzin
authors.forename: Alfred
authors.initials: A
authors.lastname: Lautwein
authors.forename: Christoph
authors.initials: C
authors.lastname: Driessen
authors.forename: Petra
authors.initials: P
authors.lastname: Schnorrer
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Weber
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.forename: Raffael
authors.initials: R
authors.lastname: Kurek
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
authors.forename: Dieter
authors.initials: D
authors.lastname: Bromme
mesh_terms: D000293:Adolescent; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000378:metabolism*; D015153:Blotting, Western; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D003546:Cysteine Endopeptidases / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007834:Lasers; D051379:Mice; D009157:Myasthenia Gravis / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; C045084:invariant chain; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C028217:cathepsin S; C117627:CTSV protein, human