Comparative quantitative mass spectrometry analysis of MHC class II-associated peptides reveals a role of GILT in formation of self-peptide repertoire.
Gamma interferon Inducible Lysosomal Thiol reductase (GILT) is a unique lysosomal reductase that reduces disulfide bonds of endocytosed proteins. Lack of GILT clearly decreases CD4 T cell-antigen specific responses against some epitopes of antigens containing disulfide bonds, but not to proteins with few or no disulfide bridges. Hence, global impact of GILT on antigen presentation is currently not well understood. We used Nano-LC-ESI-MS/MS to investigate how GILT affects diversity of self-peptides presented by MHC class II molecules. Surprisingly, the repertoire of self-peptides in the absence of GILT does not appear to be significantly different, as only few peptide species (approximately 2%) were found to be the unique indicators of GILT's presence or absence. In the absence of GILT about thirty peptide species (approximately 5%) were found either uniquely or fourteen to hundred fold more abundantly expressed than in the presence of GILT. Our data indicate that GILT has limited yet unexpected effect on self-peptide species presented by MHC class II antigens.
Bogunovic
Branka
B
Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, United States of America.
Srinivasan
Priya
P
Ueda
Yumi
Y
Tomita
York
Y
Maric
Maja
M
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000172:deficiency / Q000276:immunology*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D010455:Peptides / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D011485:Protein Binding; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D013154:Spleen / Q000201:enzymology / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D010455:Peptides; D010088:Oxidoreductases; C483811:Ifi30 protein, mouse; D050862:Oxidoreductases Acting on Sulfur Group Donors