Comparative Quantitative Mass Spectrometry Analysis of MHC Class II-Associated Peptides Reveals a Role of GILT in Formation of Self-Peptide Repertoire

被引:21
作者
Bogunovic, Branka [1 ]
Srinivasan, Priya [1 ]
Ueda, Yumi [2 ]
Tomita, York [2 ]
Maric, Maja [1 ]
机构
[1] Georgetown Univ, Sch Med, Dept Microbiol & Immunol, Washington, DC USA
[2] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Washington, DC USA
关键词
LYSOSOMAL THIOL REDUCTASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; T-CELL EPITOPE; IN-VIVO; CYSTEINE RESIDUES; BINDING PEPTIDES; OXIDATIVE STRESS; CELIAC-DISEASE; ANTIGEN; MOLECULES;
D O I
10.1371/journal.pone.0010599
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 (similar to 2%) were found to be the unique indicators of GILT's presence or absence. In the absence of GILT about thirty peptide species (similar to 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.
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页数:10
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