title: Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus.
abstract: Degradation of invariant chain (Ii) is a critical step in major histocompatibility complex class II-restricted antigen presentation. Cathepsin L was found to be necessary for Ii degradation in cortical thymic epithelial cells (cTECs), but not in bone marrow (BM)-derived antigen-presenting cells (APCs). Consequently, positive selection of CD4+ T cells was reduced. Because different cysteine proteinases are responsible for specific Ii degradation steps in cTECs and BM-derived APCs, the proteolytic environment in cells mediating positive and negative selection may be distinct. The identification of a protease involved in class II presentation in a tissue-specific manner suggests a potential means of manipulating CD4+ T cell responsiveness in vivo.
authors.affiliation: Howard Hughes Medical Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nakagawa
authors.forename: W
authors.initials: W
authors.lastname: Roth
authors.forename: P
authors.initials: P
authors.lastname: Wong
authors.forename: A
authors.initials: A
authors.lastname: Nelson
authors.forename: A
authors.initials: A
authors.lastname: Farr
authors.forename: J
authors.initials: J
authors.lastname: Deussing
authors.forename: J A
authors.initials: JA
authors.lastname: Villadangos
authors.forename: H
authors.initials: H
authors.lastname: Ploegh
authors.forename: C
authors.initials: C
authors.lastname: Peters
authors.forename: A Y
authors.initials: AY
authors.lastname: Rudensky
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D004847:Epithelial Cells / Q000201:enzymology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013950:Thymus Gland / Q000201:enzymology / Q000276:immunology*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C028217:cathepsin S