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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900921v1 183/2/945    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Costantino, C. M. Articles by Hafler, D. A. PubMed PubMed Citation Articles by Costantino, C. M. Articles by Hafler, D. A.

Cathepsin S Regulates Class II MHC Processing in Human CD4⁺ HLA-DR⁺ T Cells¹

Cristina Maria Costantino^*, Hidde L. Ploegh and David A. Hafler^2,*

^* Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115; Whitehead Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health grants.

² Address correspondence and reprint requests to Dr. David Hafler, Harvard Medical School, 77 Avenue Louis Pasteur, Room 641, Boston, MA 02115. E-mail address: dhafler{at}rics.bwh.harvard.edu

³ Abbreviations used in this paper: Ii, invariant chain; LHVS, leucine-homophenylalanine-vinyl sulfone; Cat, cathepsin; AEP, asparagine endopeptidase; EBV, Epstein-Barr Virus.