Cathepsin S regulates class II MHC processing in human CD4+ HLA-DR+ T cells
Author(s)Ploegh, Hidde; Costantino, Cristina Maria; Hafler, David A.
MetadataShow full item record
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.
July 15, 2010
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Journal of Immunology
American Association of Immunologists
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.
Author's final manuscript