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http://purl.uniprot.org/citations/20331476http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20331476http://www.w3.org/2000/01/rdf-schema#comment"

Summary

The expression of major histocompatibility complex class II (MHC II) molecules is post-translationally regulated by endocytic protein turnover. Here, we identified the serine protease cathepsin G (CatG) as an MHC II-degrading protease by in vitro screening and examined its role in MHC II turnover in vivo. CatG, uniquely among endocytic proteases tested, initiated cleavage of detergent-solubilized native and recombinant soluble MHC II molecules. CatG cleaved human leukocyte antigen (HLA)-DR isolated from both HLA-DM-expressing and DM-null cells. Even following CatG cleavage, peptide binding was retained by pre-loaded, soluble recombinant HLA-DR. MHC II cleavage occurred on the loop between fx1 and fx2 of the membrane-proximal beta2 domain. All allelic variants of HLA-DR tested and murine I-A(g7) class II molecules were susceptible, whereas murine I-E(k) and HLA-DM were not, consistent with their altered sequence at the P1' position of the CatG cleavage site. CatG effects were reduced on HLA-DR molecules with DRB mutations in the region implicated in interaction with HLA-DM. In contrast, addition of CatG to intact B-lymphoblastoid cell lines (B-LCLs) did not cause degradation of membrane-bound MHC II. Moreover, inhibition or genetic ablation of CatG in primary antigen-presenting cells did not cause accumulation of MHC II molecules. Thus, in vivo, the CatG cleavage site is sterically inaccessible or masked by associated molecules. A combination of intrinsic and context-dependent proteolytic resistance may allow peptide capture by MHC II molecules in harshly proteolytic endocytic compartments, as well as persistent antigen presentation in acute inflammatory settings with extracellular proteolysis."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.org/dc/terms/identifier"doi:10.1111/j.1365-2567.2010.03247.x"xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Hou T."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Schilling J."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Zou F."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Lau K."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Busch R."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Burster T."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Mellins E.D."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Boehm B.O."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Truong P."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Macmillan H."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Schaffert S."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/author"Strohman M."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/name"Immunology"xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/pages"436-446"xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/title"Masking of a cathepsin G cleavage site in vivo contributes to the proteolytic resistance of major histocompatibility complex class II molecules."xsd:string
http://purl.uniprot.org/citations/20331476http://purl.uniprot.org/core/volume"130"xsd:string
http://purl.uniprot.org/citations/20331476http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20331476
http://purl.uniprot.org/citations/20331476http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20331476
http://purl.uniprot.org/uniprot/#_A0A0A7C3H3-mappedCitation-20331476http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20331476
http://purl.uniprot.org/uniprot/#_A0A0A7C3I1-mappedCitation-20331476http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20331476
http://purl.uniprot.org/uniprot/#_A0A0A7C3I5-mappedCitation-20331476http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20331476
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