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Defective Antigen Processing in GILT-Free Mice

Science  09 Nov 2001:
Vol. 294, Issue 5545, pp. 1361-1365
DOI: 10.1126/science.1065500

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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.

  • * 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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