Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus.
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.
Nakagawa
T
T
Howard Hughes Medical Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Roth
W
W
Wong
P
P
Nelson
A
A
Farr
A
A
Deussing
J
J
Villadangos
J A
JA
Ploegh
H
H
Peters
C
C
Rudensky
A Y
AY
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*
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