Cathepsin S regulates class II MHC processing in human CD4+ HLA-DR+ T cells
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Ploegh_Cathepsin S.pdf
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Author(s)
Ploegh, Hidde
Costantino, Cristina Maria
Hafler, David A.
Date Issued
June 2009
Journal
Journal of Immunology
Publisher
American Association of Immunologists
Citation
Costantino, C. M., H. L. Ploegh, and D. A. Hafler. “Cathepsin S Regulates Class II MHC Processing in Human CD4+ HLA-DR+ T Cells.” The Journal of Immunology 183.2 (2009): 945–952.
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Author's final manuscript
Abstract
Although it has long been known that human CD4+ T cells can express functional class II MHC molecules, the role of lysosomal proteases in the T cell class II MHC processing and presentation pathway is unknown. Using CD4+ T cell clones that constitutively express class II MHC, we determined that cathepsin S is necessary for invariant chain proteolysis in T cells. CD4+HLA-DR+ T cells down-regulated cathepsin S expression and activity 18 h after activation, thereby ceasing nascent class II MHC product formation. This blockade resulted in the loss of the invariant chain fragment CLIP from the cell surface, suggesting that—like professional APC—CD4+ HLA-DR+ cells modulate self-Ag presentation as a consequence of activation. Furthermore, cathepsin S expression and activity, and concordantly cell surface CLIP expression, was reduced in HLA-DR+ CD4+ T cells as compared with B cells both in vitro and ex vivo.
Description
July 15, 2010
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.4049/jimmunol.0900921
