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
- 1 May 2000
- journal article
- research article
- Published by Wiley in Immunology
- Vol. 100 (1), 13-20
- https://doi.org/10.1046/j.1365-2567.2000.00000.x
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.Keywords
This publication has 31 references indexed in Scilit:
- CAPTURE AND PROCESSING OF EXOGENOUS ANTIGENS FOR PRESENTATION ON MHC MOLECULESAnnual Review of Immunology, 1997
- INDUCTION OF TH1 AND TH2 CD4+T CELL RESPONSES:The Alternative ApproachesAnnual Review of Immunology, 1997
- Functional diversity of helper T lymphocytesNature, 1996
- Enhanced Dissociation of HLA-DR-Bound Peptides in the Presence of HLA-DMScience, 1996
- Essential Role for Cathepsin S in MHC Class II–Associated Invariant Chain Processing and Peptide LoadingImmunity, 1996
- The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor-alpha beta-transgenic model.The Journal of Experimental Medicine, 1995
- Invariant chain cleavage and peptide loading in major histocompatibility complex class II vesicles.The Journal of Experimental Medicine, 1995
- MHC-dependent antigen processing and peptide presentation: Providing ligands for T lymphocyte activationCell, 1994
- Disruption of the murine IL-4 gene blocks Th2 cytokine responsesNature, 1993
- The polyclonal and antigen-specific IgE and IgG subclass response of mice injected with ovalbumin in alum or complete Freund's adjuvantCellular Immunology, 1989