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Science 17 April 1998:
Vol. 280. no. 5362, pp. 450 - 453
DOI: 10.1126/science.280.5362.450
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Reports

Cathepsin L: Critical Role in Ii Degradation and CD4 T Cell Selection in the Thymus

Terry Nakagawa, * Wera Roth, * Phillip Wong, Andrew Nelson, Andrew Farr, Jan Deussing, Jose A. Villadangos, Hidde Ploegh, Christoph Peters, Alexander Y. Rudensky dagger

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.

T. Nakagawa, P. Wong, A. Y. Rudensky, Howard Hughes Medical Institute and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
W. Roth, J. Deussing, C. Peters, Medizinische Molekularbiologie, Abteilung Heamatologie-Onkologie, Klinikum der Albert-Ludwigs-Universitat Freiburg, 79106 Freiburg, Germany.
A. Nelson and A. Farr, Department of Biological Structure and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
J. A. Villadangos and H. Ploegh, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed: E-mail: sasha{at}nucleus.immunol.washington.edu

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Developmental plasticity of CNS microglia.
L. Santambrogio, S. L. Belyanskaya, F. R. Fischer, B. Cipriani, C. F. Brosnan, P. Ricciardi-Castagnoli, L. J. Stern, J. L. Strominger, and R. Riese (2001)
PNAS 98, 6295-6300
   Abstract »    Full Text »    PDF »
Dynamic Tuning of T Cell Reactivity by Self-Peptide-Major Histocompatibility Complex Ligands.
P. Wong, G. M. Barton, K. A. Forbush, and A. Y. Rudensky (2001)
J. Exp. Med. 193, 1179-1188
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Cytokines Regulate Proteolysis in Major Histocompatibility Complex Class II-Dependent Antigen Presentation by Dendritic Cells.
E. Fiebiger, P. Meraner, E. Weber, I-F. Fang, G. Stingl, H. Ploegh, and D. Maurer (2001)
J. Exp. Med. 193, 881-892
   Abstract »    Full Text »    PDF »
Dissociation of thymic positive and negative selection in transgenic mice expressing major histocompatibility complex class I molecules exclusively on thymic cortical epithelial cells.
M. Capone, P. Romagnoli, F. Beermann, H. R. MacDonald, and J. P. M. van Meerwijk (2001)
Blood 97, 1336-1342
   Abstract »    Full Text »    PDF »
An Incremental Increase in the Complexity of Peptides Bound to Class II MHC Changes the Diversity of Positively Selected {{alpha}}{{beta}} TCRs.
R. Pacholczyk, P. Kraj, and L. Ignatowicz (2001)
J. Immunol. 166, 2357-2363
   Abstract »    Full Text »    PDF »
On the Self-Referential Nature of Naive MHC Class II-Restricted T Cells.
C. Viret, X. He, and C. A. Janeway Jr. (2000)
J. Immunol. 165, 6183-6192
   Abstract »    Full Text »    PDF »
Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling.
W. ROTH, J. DEUSSING, V. A. BOTCHKAREV, M. PAULY-EVERS, P. SAFTIG, A. HAFNER, P. SCHMIDT, W. SCHMAHL, J. SCHERER, I. ANTON-LAMPRECHT, et al. (2000)
FASEB J 14, 2075-2086
   Abstract »    Full Text »
TCR Signaling for Initiation and Completion of Thymocyte Positive Selection Has Distinct Requirements for Ligand Quality and Presenting Cell Type.
K. Yasutomo, B. Lucas, and R. N. Germain (2000)
J. Immunol. 165, 3015-3022
   Abstract »    Full Text »    PDF »
The HLA System- First of Two Parts.
J. Klein and A. Sato (2000)
N. Engl. J. Med. 343, 702-709
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Opening a Window on Thymic Positive Selection: Developmental Changes in the Influence of Cosignaling by Integrins and CD28 on Selection Events Induced by TCR Engagement.
B. Lucas and R. N. Germain (2000)
J. Immunol. 165, 1889-1895
   Abstract »    Full Text »    PDF »
Phagosomes Acquire Nascent and Recycling Class II MHC Molecules but Primarily Use Nascent Molecules in Phagocytic Antigen Processing.
L. Ramachandra and C. V. Harding (2000)
J. Immunol. 164, 5103-5112
   Abstract »    Full Text »    PDF »
Cytoplasmic Processing Is a Prerequisite for Presentation of an Endogenous Antigen by Major Histocompatibility Complex Class II Proteins.
J. D. Lich, J. F. Elliott, and J. S. Blum (2000)
J. Exp. Med. 191, 1513-1524
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Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages.
G.-P. Shi, R. A.R. Bryant, R. Riese, S. Verhelst, C. Driessen, Z. Li, D. Bromme, H. L. Ploegh, and H. A. Chapman (2000)
J. Exp. Med. 191, 1177-1186
   Abstract »    Full Text »    PDF »
Alternative Proteolytic Processing of Mouse Mammary Tumor Virus Superantigens.
F. Denis, N. H. Shoukry, M. Delcourt, J. Thibodeau, N. Labrecque, H. McGrath, J. S. Munzer, N. G. Seidah, and R.-P. Sékaly (2000)
J. Virol. 74, 3067-3073
   Abstract »    Full Text »
Dipeptidyl Peptidase I Cleaves Matrix-Associated Proteins and Is Expressed Mainly by Mast Cells in Normal Dog Airways.
P. J. Wolters, M. Laig-Webster, and G. H. Caughey (2000)
Am. J. Respir. Cell Mol. Biol. 22, 183-190
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Bacterial Proteins Can Be Processed by Macrophages in a Transporter Associated with Antigen Processing-Independent, Cysteine Protease-Dependent Manner for Presentation by MHC Class I Molecules.
D. J. Campbell, T. Serwold, and N. Shastri (2000)
J. Immunol. 164, 168-175
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The HSC73 Molecular Chaperone: Involvement in MHC Class II Antigen Presentation.
N. Panjwani, O. Akbari, S. Garcia, M. Brazil, and B. Stockinger (1999)
J. Immunol. 163, 1936-1942
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Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo.
C. T. N. Pham and T. J. Ley (1999)
PNAS 96, 8627-8632
   Abstract »    Full Text »    PDF »
Cutting Edge: Immunoregulation of Th Cells by Naturally Processed Peptide Antagonists.
R. T. Carson, D. D. Desai, K. M. Vignali, and D. A. A. Vignali2 (1999)
J. Immunol. 162, 1-4
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Fc{epsilon} Receptor I on Dendritic Cells Delivers IgE-Bound Multivalent Antigens into a Cathepsin S-Dependent Pathway of MHC Class II Presentation.
D. Maurer, E. Fiebiger, B. Reininger, C. Ebner, P. Petzelbauer, G.-P. Shi, H. A. Chapman, and G. Stingl (1998)
J. Immunol. 161, 2731-2739
   Abstract »    Full Text »    PDF »


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