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PubMed · 11701933

Defective antigen processing in GILT-free mice.

M Maric·B Arunachalam·U T Phan·C Dong·W S Garrett·K S Cannon·C Alfonso·L Karlsson·R A Flavell·P Cresswell
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Abstract

Processing of proteins for major histocompatibility complex (MHC) class II-restricted presentation to CD4-positive T lymphocytes occurs after they are internalized by antigen-presenting cells (APCs). Antigenic proteins frequently contain disulfide bonds, and their reduction in the endocytic pathway facilitates processing. In humans, a gamma interferon-inducible lysosomal thiol reductase (GILT) is constitutively present in late endocytic compartments of APCs. Here, we identified the mouse homolog of GILT and generated a GILT knockout mouse. GILT facilitated the processing and presentation to antigen-specific T cells of protein antigens containing disulfide bonds. The response to hen egg lysozyme, a model antigen with a compact structure containing four disulfide bonds, was examined in detail.

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Amino Acid SequenceAnimalsAntigen PresentationAntigen-Presenting CellsAntigensCell LineDendritic CellsDisulfidesEpitopesHistocompatibility Antigens Class IIHybridomasHydrogen-Ion ConcentrationImmunizationMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataMuramidaseOxidoreductasesOxidoreductases Acting on Sulfur Group DonorsProtein ConformationProtein FoldingSpleenT-LymphocytesJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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M Maric, B Arunachalam, U T Phan, C Dong, W S Garrett, K S Cannon, C Alfonso, L Karlsson, R A Flavell, P Cresswell. 2001-11-09. Defective antigen processing in GILT-free mice.. https://doi.org/10.1126/science.1065500

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