Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Cathepsin S activity regulates antigen presentation and immunity.
R J Riese, … , H L Ploegh, H A Chapman
R J Riese, … , H L Ploegh, H A Chapman
Published June 1, 1998
Citation Information: J Clin Invest. 1998;101(11):2351-2363. https://doi.org/10.1172/JCI1158.
View: Text | PDF
Research Article Article has an altmetric score of 7

Cathepsin S activity regulates antigen presentation and immunity.

  • Text
  • PDF
Abstract

MHC class II molecules display antigenic peptides on cell surfaces for recognition by CD4(+) T cells. Proteolysis is required in this process both for degradation of invariant chain (Ii) from class II-Ii complexes to allow subsequent binding of peptides, and for generation of the antigenic peptides. The cysteine endoprotease, cathepsin S, mediates Ii degradation in human and mouse antigen-presenting cells. Studies described here examine the functional significance of cathepsin S inhibition on antigen presentation and immunity. Specific inhibition of cathepsin S in A20 cells markedly impaired presentation of an ovalbumin epitope by interfering with class II-peptide binding, not by obstructing generation of the antigen. Administration of a cathepsin S inhibitor to mice in vivo selectively inhibited activity of cathepsin S in splenocytes, resulting in accumulation of a class II-associated Ii breakdown product, attenuation of class II-peptide complex formation, and inhibition of antigen presentation. Mice treated with inhibitor had an attenuated antibody response when immunized with ovalbumin but not the T cell-independent antigen TNP-Ficoll. In a mouse model of pulmonary hypersensitivity, treatment with the inhibitor also abrogated a rise in IgE titers and profoundly blocked eosinophilic infiltration in the lung. Thus, inhibition of cathepsin S in vivo alters Ii processing, antigen presentation, and immunity. These data identify selective inhibition of cysteine proteases as a potential therapeutic strategy for asthma and autoimmune disease processes.

Authors

R J Riese, R N Mitchell, J A Villadangos, G P Shi, J T Palmer, E R Karp, G T De Sanctis, H L Ploegh, H A Chapman

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1991 Total
Citations: 3 5 5 11 12 10 4 9 19 7 10 6 11 2 18 8 8 16 12 7 9 10 12 12 7 13 13 1 1 261
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2018 (9)

Title and authors Publication Year
NOD and NOR mice exhibit comparable development of lacrimal gland secretory dysfunction but NOD mice have more severe autoimmune dacryoadenitis
Y Ju, SR Janga, W Klinngam, JA MacKay, D Hawley, D Zoukhri, MC Edman, SF Hamm-Alvarez
Experimental Eye Research 2018
Cysteine protease cathepsins in cardiovascular disease: from basic research to clinical trials
CL Liu, J Guo, X Zhang, GK Sukhova, P Libby, GP Shi
Nature Reviews Cardiology 2018
Cysteine cathepsins as a prospective target for anticancer therapies—current progress and prospects
A Pogorzelska, B Żołnowska, R Bartoszewski
Biochimie 2018
Class II MHC antigen processing in immune tolerance and inflammation
MM Jurewicz, LJ Stern
Immunogenetics 2018
Effects of Cross-Presentation, Antigen Processing, and Peptide Binding in HIV Evasion of T Cell Immunity
BF Frey, J Jiang, Y Sui, LF Boyd, B Yu, G Tatsuno, R Billeskov, S Solaymani-Mohammadi, PW Berman, DH Margulies, JA Berzofsky
Journal of immunology (Baltimore, Md. : 1950) 2018
Engineered hybrid spider silk particles as delivery system for peptide vaccines
M Lucke, I Mottas, T Herbst, C Hotz, L Römer, M Schierling, HM Herold, U Slotta, T Spinetti, T Scheibel, G Winter, C Bourquin, J Engert
Biomaterials 2018
Long-term dietary replacement of fishmeal and fish oil in diets for rainbow trout (Oncorhynchus mykiss): Effects on growth, whole body fatty acids and intestinal and hepatic gene expression
V Lazzarotto, F Médale, L Larroquet, G Corraze, S Martínez-Llorens
PloS one 2018
Immune effects of the neurotoxins ciguatoxins and brevetoxins
O Pierre, L Misery, M Talagas, RL Garrec
Toxicon : official journal of the International Society on Toxinology 2018
Proteomic analysis of lipopolysaccharide activated human monocytes
M Lausen, TB Poulsen, G Christiansen, K Kastaniegaard, A Stensballe, S Birkelund
Molecular Immunology 2018

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 1 X users
Referenced in 38 patents
126 readers on Mendeley
See more details