comparative quantitative mass spectrometry analysis of mhc class ii-associated peptides reveals a role of gilt in formation of self-peptide repertoire类ii-associated肽mhc的比较定量质谱分析揭示了一个镀金的角色活动形成的曲目.pdf

Comparative Quantitative Mass Spectrometry Analysis of MHC Class II-Associated Peptides Reveals a Role of GILT in Formation of Self-Peptide Repertoire 1 1 2 2 1 Branka Bogunovic , Priya Srinivasan , Yumi Ueda , York Tomita , Maja Maric * 1 Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, D. C., United States of America, 2 Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, D. C., United States of America Abstract 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 (,2%) were found to be the unique indicators of GILT’s presence or absence. In the absence of GILT about thirty peptide species (,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. Citation: Bogunovic B, Srinivasan P, Ueda Y, Tomita Y, Maric M (2010) Comparative Quantitative Mass Spectrometry Analysis of MHC Class II-Associated Peptides Reveals a Role of GILT in Formation of Self-Peptide Repertoi