© The Rockefeller University Press, 0022-1007/2000/3/1057/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 6, March 20, 2000 1057-1062
Invariant Chain Controls H2-M Proteolysis in Mouse Splenocytes and Dendritic Cells
Philippe Pierrea,
Idit Shacharb,c,
Didi Matzac,
Evelina Gattia,
Richard A. Flavellb, and
Ira Mellmana
a Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research,
b Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8002
c Department of Immunology, The Weizmann Institute of Sciences, Rehovot, Israel 76100
Correspondence to:
Ira Mellman, Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, P.O. Box 208002, 333 Cedar St., New Haven, CT 06520-8002. Tel:203-785-4303 Fax:203-785-4301 E-mail:ira.mellman{at}yale.edu.
Released online: 20 March 2000
The association of invariant (Ii) chain with major histocompatibility complex (MHC) class II dimers is required for proper antigen presentation to T cells by antigen-presenting cells. Mice lacking Ii chain have severe abnormalities in class II transport, T cell selection, and B cell maturation. We demonstrate here that H2-M, which is required for efficient class II antigenic peptide loading, is unexpectedly downregulated in splenocytes and mature dendritic cells (DCs) from Ii-/- mice. Downregulation reflects an increased rate of degradation in Ii-/- cells. Degradation apparently occurs within lysosomes, as it is prevented by cysteine protease inhibitors such as E64, but not by the proteasome inhibitor lactacystin. Thus, Ii chain may act as a lysosomal protease inhibitor in B cells and DCs, with its deletion contributing indirectly to the loss of H2-M.
Key Words:
invariant chain, H2-M, DM, cathepsin, dendritic cell
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