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


El-Sukkari, D; Wilson, NS; Hakansson, K; Steptoe, RJ; Grubb, A; Shortman, K; Villadangos, JA
2003-11-15
JOURNAL OF IMMUNOLOGY
Journal Article
171
10
5003-5011
Dendritic cells (DC) undergo complex developmental changes during maturation. The MHC class H (MHC H) 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 H chaperone E, and hence in the formation of MHC H-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 H peptide loading proceeded similarly in all three DC populations. We then analyzed MHC H 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.
AMER ASSOC IMMUNOLOGISTS
MHC CLASS-II; INVARIANT CHAIN DEGRADATION; CATHEPSIN-S; DEVELOPMENTAL REGULATION; INFLAMMATORY STIMULI; SURFACE EXPRESSION; AMYLOID ANGIOPATHY; MOUSE; MOLECULES; MATURATION
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Creation Date 2003-11-15 12:00:00