Publication

Individual cathepsins degrade immune complexes internalized by antigen-presenting cells via Fcgamma receptors

Journal Paper/Review - May 1, 2001

Units
PubMed
Doi

Citation
Driessen C, Lennon-Dumenil A, Ploegh H. Individual cathepsins degrade immune complexes internalized by antigen-presenting cells via Fcgamma receptors. European journal of immunology 2001; 31:1592-601.
Type
Journal Paper/Review (English)
Journal
European journal of immunology 2001; 31
Publication Date
May 1, 2001
Issn Print
0014-2980
Pages
1592-601
Brief description/objective

We have analyzed the intracellular degradation of an immune complex after its FcgammaR-mediated uptake in antigen-presenting cells (APC). Mice that lack the cathepsins (Cat) S, L, B and D allowed us to assess the direct contribution of these individual proteases to the processing events observed. CatS and CatB mediate the bulk of degradation of the Ig-125I-labeled F(ab')2 immune complex delivered via FcgammaR, while CatL and CatD are dispensable. CatS and CatB are involved in independent processing pathways and can substitute in part for each other's absence. The combined ablation of both proteases reduces the rate of degradation observed by > 80 %. CatB is required for the generation of F(ab')23, a predominant degradation intermediate smaller by approximately 3 kDa than the 125I-labeled F(ab')2 itself. In addition, absence of CatB in vivo significantly affects the activity pattern of the remaining cysteine proteases. Thus, we conclude that CatB is a key enzyme for the proper degradation of an immune complex taken up by FcgammaR and for the control of protease activity in the endocytic pathway of APC.