Cathepsin S regulates the expression of cathepsin L and the turnover of gamma-interferon-inducible lysosomal thiol reductase in B lymphocytes.
Loading of antigenic peptide fragments on major histocompatibility complex class II molecules is essential for generation of CD4(+) T cell responses and occurs after cathepsin-mediated degradation of the invariant chain chaperone molecule. Cathepsins are expressed differentially in antigen presenting cells, and mice deficient in cathepsin S or cathepsin L exhibit severely impaired antigen presentation in peripheral lymphoid organs and the thymus, respectively. To determine whether these defects are due solely to the block in invariant chain cleavage, we used cathepsin-deficient B cells to examine the role of cathepsins S and B in the degradation of other molecules important in the class II presentation pathway. Our data indicate that neither cathepsin S nor B is critical for H-2M degradation or processing of precursor gamma-interferon-inducible lysosomal thiol reductase (GILT) to a mature thiol reductase, but suggest a role for cathepsin S in the turnover of mature GILT and in regulating levels of mature cathepsin L protein in B cells. Despite the presence of mature cathepsin L protein, no enzyme activity could be detected in B cells or dendritic cells. These experiments suggest a novel mechanism by which these functionally important enzymes may be regulated.
Honey
K
K
Department of Immunology and the Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98115, USA.
Duff
M
M
Beers
C
C
Brissette
W H
WH
Elliott
E A
EA
Peters
C
C
Maric
M
M
Cresswell
P
P
Rudensky
A
A
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D001483:Base Sequence; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D017931:DNA Primers; D003713:Dendritic Cells / Q000201:enzymology; D010450:Endopeptidases; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D010088:Oxidoreductases / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors
D015853:Cysteine Proteinase Inhibitors; D017931:DNA Primers; D010088:Oxidoreductases; C483811:Ifi30 protein, mouse; D050862:Oxidoreductases Acting on Sulfur Group Donors; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C028217:cathepsin S