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Publication : The protease inhibitor cystatin C is differentially expressed among dendritic cell populations, but does not control antigen presentation.

First Author  El-Sukkari D Year  2003
Journal  J Immunol Volume  171
Issue  10 Pages  5003-11
PubMed ID  14607896 Mgi Jnum  J:119164
Mgi Id  MGI:3701393 Doi  10.4049/jimmunol.171.10.5003
Citation  El-Sukkari D, et al. (2003) The protease inhibitor cystatin C is differentially expressed among dendritic cell populations, but does not control antigen presentation. J Immunol 171(10):5003-11
abstractText  Dendritic cells (DC) undergo complex developmental changes during maturation. The MHC class II (MHC II) molecules of immature DC accumulate in intracellular compartments, but are expressed at high levels on the plasma membrane upon DC maturation. It has been proposed that the cysteine protease inhibitor cystatin C (CyC) plays a pivotal role in the control of this process by regulating the activity of cathepsin S, a protease involved in removal of the MHC II chaperone Ii, and hence in the formation of MHC II-peptide complexes. We show that CyC is differentially expressed by mouse DC populations. CD8(+) DC, but not CD4(+) or CD4(-)CD8(-) DC, synthesize CyC, which accumulates in MHC II(+)Lamp(+) compartments. However, Ii processing and MHC II peptide loading proceeded similarly in all three DC populations. We then analyzed MHC II localization and Ag presentation in CD8(+) DC, bone marrow-derived DC, and spleen-derived DC lines, from CyC-deficient mice. The absence of CyC did not affect the expression, the subcellular distribution, or the formation of peptide-loaded MHC II complexes in any of these DC types, nor the efficiency of presentation of exogenous Ags. Therefore, CyC is neither necessary nor sufficient to control MHC II expression and Ag presentation in DC. Our results also show that CyC expression can differ markedly between closely related cell types, suggesting the existence of hitherto unrecognized mechanisms of control of CyC expression.
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