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Published on: June 3, 2012
Mapping Influenza-Induced Posttranslational Modifications on Histones from CD8+ T Cells
Svetlana Rezinciuc1, Zhixin Tian2, Si Wu2
1Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
This study introduces a new mass spectrometry method, HiPTMap, to map histone posttranslational modifications (PTMs) in CD8 T cells. HiPTMap reveals significant changes in histone PTMs during influenza infection, impacting T cell function.
Area of Science:
- Immunology
- Proteomics
- Epigenetics
Background:
- T cell function relies on epigenetic regulation, including histone posttranslational modifications (PTMs).
- Traditional mass spectrometry (MS) methods have limitations in comprehensively identifying histone PTMs.
- Understanding dynamic PTM changes is crucial for T cell responses.
Purpose of the Study:
- To develop and validate a novel mass spectrometry approach for comprehensive histone proteoform analysis.
- To identify and quantify histone PTMs in CD8 T cells during influenza infection.
- To investigate the impact of infection and T cell activation on histone modifications.
Main Methods:
- Utilized online two-dimensional liquid chromatography-tandem MS (2D LC-MS/MS) with alternating electron transfer dissociation (ETD) and collision-induced dissociation (CID).
- Employed reversed-phase liquid chromatography (RPLC) and weak cation exchange hydrophilic interaction liquid chromatography (WCX-HILIC) for separation.
- Developed the histone-intact protein PTM mapping (HiPTMap) strategy for proteoform identification and quantification.
Main Results:
- HiPTMap successfully identified and quantified histone proteoforms in CD8 T cells.
- Influenza infection significantly altered histone PTMs, with changes observed during T cell migration.
- Responding T cells exhibited increased transcription-enhancing modifications during secondary infections.
Conclusions:
- The HiPTMap method provides a powerful tool for deep profiling of histone PTMs.
- Dynamic changes in histone PTMs are critical for CD8 T cell responses to viral infections.
- Epigenetic reprogramming of T cells is essential for effective immunity.
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