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.
Maric
M
M
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Arunachalam
B
B
Phan
U T
UT
Dong
C
C
Garrett
W S
WS
Cannon
K S
KS
Alfonso
C
C
Karlsson
L
L
Flavell
R A
RA
Cresswell
P
P
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology*; D000941:Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000201:enzymology; D004220:Disulfides / Q000737:chemistry; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006825:Hybridomas; D006863:Hydrogen-Ion Concentration; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011487:Protein Conformation; D017510:Protein Folding; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D004220:Disulfides; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010088:Oxidoreductases; C483811:Ifi30 protein, mouse; D050862:Oxidoreductases Acting on Sulfur Group Donors; C421864:hen egg lysozyme; D009113:Muramidase