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 a nd occurs after cathepsin mediated degradation of the invariant chain chape rone molecule. Cathepsins are expressed differentially in antigen presentin g 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 blo ck in invariant chain cleavage, we used cathepsin-deficient B cells to exam ine the role of cathepsins S and E in the degradation of other molecules im portant in the class II presentation pathway. Our data indicate that neithe r cathepsin S nor B is critical for H-2M degradation or processing of precu rsor gamma -interferon inducible lysosomal thiol reductase (GILT) to a matu re thiol reductase, but suggest a role for cathepsin S in the turnover of m ature GILT and in regulating levels of mature cathepsin L protein in E cell s. Despite the presence of mature cathepsin L protein, no enzyme activity c ould be detected in B cells or dendritic cells. These experiments suggest a novel mechanism by which these functionally important enzymes may be regul ated.