The protease inhibitor cystatin C is differentially expressed among dendritic cell populations, but does not control antigen presentation.
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.
El-Sukkari
Dima
D
The Walter and Eliza Hall Institute of Medical Research, Victoria, Melbourne, Australia.
Wilson
Nicholas S
NS
Hakansson
Katarina
K
Steptoe
Raymond J
RJ
Grubb
Anders
A
Shortman
Ken
K
Villadangos
José A
JA
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002403:Cathepsins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D055316:Cystatin C; D015891:Cystatins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000096:biosynthesis* / Q000502:physiology*; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; C525031:Cst3 protein, mouse; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; C045084:invariant chain; D002403:Cathepsins; C028217:cathepsin S