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Maja Maric,1Balasubramanian Arunachalam,1*Uyen T. Phan,1Chen Dong,1Wendy S. Garrett,1Kurt S. Cannon,1Christopher Alfonso,2Lars Karlsson,2Richard A. Flavell,1Peter Cresswell1§
Processing of proteins for major histocompatibility complex
(MHC) class II-restricted presentation to CD4-positive T
lymphocytesoccurs 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 compartmentsof APCs. Here, we identified the mouse homolog of GILT and generateda
GILT knockout mouse. GILT facilitated the processing and presentationto antigen-specific T cells of protein antigens containing disulfidebonds. The response to hen egg lysozyme, a model antigen witha compact
structure containing four disulfide bonds, was examinedin detail.
1 Section of Immunobiology, Howard Hughes
Medical Institute, Yale University School of Medicine, New Haven, CT
06520, USA.
2 R. W. Johnson Pharmaceutical
Research Institute, 3210 Merryfield Row, San Diego, CA 92121, USA.
*
Present address: Aventis Pasteur, Discovery Drive, Route 611, Swiftwater, PA 18370, USA.
Present address: Department of Immunology, University
of Washington, 1959 N.E. Pacific Street, Seattle, WA 98195, USA.
Present address: Department of Immunology, Scripps
Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037,USA.
§
To whom correspondence should be addressed. E-mail:
peter.cresswell{at}yale.edu
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