Lysosomal cathepsin B plays an important role in antigen processing, while cathepsin D is involved in degradation of the invariant chain in
ovalbumin‐immunized mice

Abstract

We previously reported that CA074, a specific inhibitor of cathepsin B, modulates specific immune responses from the T helper 2 (Th2) type to Th1 type in BALB/c mice infected with Leishmania major. In the present study, we found that a similar type of immune deviation was also induced in mice immunized with ovalbumin (OVA). However, treatment of mice with pepstatin A, a specific cathepsin D inhibitor, suppressed the OVA-specific proliferation of lymphocytes and blocked the development of both Th1 and Th2 cellular responses. These inhibitors did not appear to have any direct influence in vitro on functions of naive lymphocytes. OVA antigen (47 000 MW) was digested mainly into 40 000 MW protein in vitro by lysosomal proteases from naive BALB/c mice, and its digestion was markedly inhibited by the addition of CA074, but not by addition of pepstatin A, during incubation. However, pepstatin A strongly suppressed the degradation of the major histocompatibility complex class II-associated invariant chain (Ii) molecule in vivo and in vitro. Thus, cathepsin B appears to process antigens directed to preferential activation of Th2 cells, while cathepsin D may be responsible for the degradation of Ii, the processing of which is essential in initiating the antigen-specific activation of Th1 and Th2 CD4+ T cells. These lysosomal proteases may have different functions in regulating immune responses.

Nippocystatin, a Cysteine Protease Inhibitor fromNippostrongylus brasiliensis, Inhibits Antigen Processing and Modulates Antigen-Specific Immune Response

“…Our results strongly suggest that nippocystatin secreted by N. brasiliensis during infection modifies host immune responses by interfering with antigen processing. Another possibility is that nippocystatin inhibits degradation of invariant chains or degradation of other molecules crucial for the development of some types of antigen-specific responses (4,29,33). At present, the precise mechanism of immune suppression exerted by the protein is not clear.…”

“…After digestion, samples were separated by SDS-PAGE and detected by CBB staining. The ML fraction was prepared by using a previously described protocol (33).…”

“…Members of family 2 (cystatin family) are secretion type proteins that have a single domain with a molecular mass of 13 to 15 kDa. In nematodes, members of this family have been found in Caenorhabditis elegans (33) and in some species of filariae (7,8,9,13). Recombinant cystatin of the filaria Acanthocheilonema viteae reportedly suppresses T-cell proliferation, but this suppression seems to be nonspecific, since proliferation of T lymphocytes stimulated with concanavalin A (ConA) or anti-CD3 is suppressed (9).…”

Cathespin H Is an Fgf10 Target Involved in Bmp4 Degradation during Lung Branching Morphogenesis

“…3 Thus, Ctsh may be part of a developmental program that is initially suppressed in primary buds by early signals, such as endogenous RA, but is later released during branching morphogenesis. blocking of cathepsin function in vivo and in vitro (9,24,35). Presently, there is only one inhibitor proven to be selective for Ctsh.…”

Subcloning and Expression of Functional Human Cathepsin B and K in E. coli: Characterization and Inhibition by Flavonoids

“…Cathepsin B is the most abundant in all of the cysteine proteases (Kirschke et al, 1995). Cathepsin B participates in many diverse cellular processes including protein degradation, antigen processing (Zhang et al, 2000), and apoptosis (Bien et al, 2010;Chwieralski et al, 2006;Roberts et al, 1999). It has been implicated in a variety of diseases including cancer invasion and metastasis (Ledakis et al, 1996;Matarrese et al, 2010;Roshy et al, 2003;Sinha et al, 2001;Szpaderska and Frankfater, 2001;Yan et al, 1998), angiogenesis (Im et al, 2005;Kruszewski et al, 2004;Malla et al, 2011;Sinha et al, 1995), inflammation (Hashimoto et al, 2001;Kakegawa et al, 2004), and Alzheimer's Disease (Gan et al, 2004;Hook, 2006;Hook et al, 2008).…”