Induction of a productive T cell response (two, 3). At the least some elements of cytokine-induced DC maturation are counteracted by antiinflammatory stimuli (4). Within the MHC class II REV-ERB Proteins medchemexpress presentation pathway, lysosomal proteases of the cathepsin (cat) household handle the processing of Ag and the formation of peptide-receptive class II dimers (5). The nature of those cats is a matter of debate. Precise proteases may be devoted towards the presentation of specific Ags: asparaginyl endopeptidase is involved inside the degradation of tetanus toxin by B lymphoblasts (six). While the role of this protease in human DCs remains to be established, it is affordable to recommend that more proteases are important for Ag degradation. In actual fact, catB is viewed as an exopeptidase responsible for the degradation of peptides, proteins, toxins, and cell surface receptors that enter the cell by way of endo- or phagocytosis (7). The digestion on the invariant chain (Ii) is really a central stepE. Fiebiger and P. Meraner contributed equally to this function. Address correspondence to Dieter Maurer, Department of Dermatology/CeMM, University of Vienna Health-related College, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Telephone: 43-1-40400-7769; Fax: 43-14031-900; E-mail: [email protected] 1Abbreviations applied in this paper: cat, cathepsin; CLIP, class II ssociated Ii-derived peptide; Cy C, cystatin C; DC, dendritic cell; HLA, histocompatibility leukocyte antigen; Ii, invariant chain; LHVS, N-morpholinurealeucine-homophenylalanine-vinylsulfone-phenyl; LIP, leupeptin-induced Ii peptide; md, monocyte-derived; MFI, imply fluorescence intensity; OG, oregon green; SLIP, tiny leupeptin-induced Ii peptide; TCC, T cell clone; TT, tetanus toxoid.J. Exp. Med. The Rockefeller University Press 0022-1007/2001/04/881/12 5.00 Volume 193, Quantity eight, April 16, 2001 88192 http://www.jem.org/cgi/content/full/193/8/in class II ependent Ag presentation, since it can be a prerequisite for the formation of peptide-occupied SDS steady class dimers. The stepwise proteolytic degradation of Ii in II endo/lysosomal compartments generates a heterogeneous set of 3-kD fragments, Thy-1/CD90 Proteins Molecular Weight termed class II ssociated Ii-derived peptides (CLIPs), which remain bound for the class II binding groove till exchanged for antigenic peptides within a histocompatibility leukocyte Ag (HLA)-DM ependent fashion (5, ten, 11). catS is the most potent catalyst from the CLIP generation in vitro and in vivo (125). Additional potential candidate enzymes are catF, catB, catD, and catL, which degrade Ii in vitro (16). catF can degrade Ii in catSdeficient murine macrophages (17), whereas catD and catB unlikely are involved inside the CLIP generation in murine cells (13, 16). catL will be the pivotal enzyme for Ii degradation in thymic epithelial cells and, therefore, is required for optimistic collection of CD4 thymocytes (18). The expression levels of various cat family members are upregulated by IL-4 and IFN- (16, 19, 20), each of which are potent inducers of class II expression in distinctive cell types. Stimuli that induce DC maturation may also regulate the activity of proteases relevant for the generation of exogenous Ag-derived peptides and proteases that are responsible for the generation of SDS steady class II dimers. Along these lines, it has been recommended that the regulation of cystatin C (Cy C) levels in DCs controls the activity of catS in the course of maturation (21). The effects imposed by antiinflammatory stimuli on DC function may likewise act by controlling the.
