The major histocompatibility complex (MHC) class II–associated invariant chain (Ii) regulates intracellular trafficking and peptide loading of MHC class II molecules. Such loading occurs after endosomal degradation of the invariant chain to a ∼3-kD peptide termed CLIP (class II–associated invariant chain peptide). Cathepsins L and S have both been implicated in degradation of Ii to CLIP in thymus and peripheral lymphoid organs, respectively. However, macrophages from mice deficient in both cathepsins S and L can process Ii and load peptides onto MHC class II dimers normally. Both processes are blocked by a cysteine protease inhibitor, indicating the involvement of an additional Ii-processing enzyme(s). Comparison of cysteine proteases expressed by macrophages with those found in splenocytes and dendritic cells revealed two enzymes expressed exclusively in macrophages, cathepsins Z and F. Recombinant cathepsin Z did not generate CLIP from Ii–MHC class II complexes, whereas cathepsin F was as efficient as cathepsin S in CLIP generation. Inhibition of cathepsin F activity and MHC class II peptide loading by macrophages exhibited similar specificity and activity profiles. These experiments show that cathepsin F, in a subset of antigen presenting cells (APCs), can efficiently degrade Ii. Different APCs can thus use distinct proteases to mediate MHC class II maturation and peptide loading.
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3 April 2000
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April 03 2000
Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages
Guo-Ping Shi,
Guo-Ping Shi
aDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Harvard Medical School, Boston, Massachusetts 02115
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Rebecca A.R. Bryant,
Rebecca A.R. Bryant
bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115
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Richard Riese,
Richard Riese
aDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Harvard Medical School, Boston, Massachusetts 02115
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Steven Verhelst,
Steven Verhelst
bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115
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Christoph Driessen,
Christoph Driessen
bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115
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Zhenqiang Li,
Zhenqiang Li
cDepartment of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029
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Dieter Bromme,
Dieter Bromme
cDepartment of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029
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Hidde L. Ploegh,
Hidde L. Ploegh
bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115
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Harold A. Chapman
Harold A. Chapman
aDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Harvard Medical School, Boston, Massachusetts 02115
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Guo-Ping Shi
aDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Harvard Medical School, Boston, Massachusetts 02115
Rebecca A.R. Bryant
bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115
Richard Riese
aDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Harvard Medical School, Boston, Massachusetts 02115
Steven Verhelst
bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115
Christoph Driessen
bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115
Zhenqiang Li
cDepartment of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029
Dieter Bromme
cDepartment of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029
Hidde L. Ploegh
bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115
Harold A. Chapman
aDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Harvard Medical School, Boston, Massachusetts 02115
Abbreviations used in this paper: Cat, cathepsin; CLIP, class II–associated invariant chain peptide; Ii, invariant chain.
Received:
October 22 1999
Revision Requested:
January 13 2000
Accepted:
January 27 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (7): 1177–1186.
Article history
Received:
October 22 1999
Revision Requested:
January 13 2000
Accepted:
January 27 2000
Citation
Guo-Ping Shi, Rebecca A.R. Bryant, Richard Riese, Steven Verhelst, Christoph Driessen, Zhenqiang Li, Dieter Bromme, Hidde L. Ploegh, Harold A. Chapman; Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages. J Exp Med 3 April 2000; 191 (7): 1177–1186. doi: https://doi.org/10.1084/jem.191.7.1177
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