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Defective antigen processing in GILT-free mice.

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.

Pubmed ID: 11701933

Authors

  • Maric M
  • Arunachalam B
  • Phan UT
  • Dong C
  • Garrett WS
  • Cannon KS
  • Alfonso C
  • Karlsson L
  • Flavell RA
  • Cresswell P

Journal

Science (New York, N.Y.)

Publication Data

November 9, 2001

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI23081

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • Antigen-Presenting Cells
  • Antigens
  • Cell Line
  • Dendritic Cells
  • Disulfides
  • Epitopes
  • Histocompatibility Antigens Class II
  • Hybridomas
  • Hydrogen-Ion Concentration
  • Immunization
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Muramidase
  • Oxidoreductases
  • Protein Conformation
  • Protein Folding
  • Spleen
  • T-Lymphocytes