Targeted identification of epigenetic determinants of T cell memory
EMSL Project ID
34940
Abstract
The ability to recognize previously encountered pathogens and rapidly eliminate them is critical to the immune system, as well as vaccine efficacy. A minute fraction of the millions of T cells circulating in the body recognize a specific pathogen, thereby endowing the entire population of T cells with protection against a diverse mixture of microbial pathogens. Following T cell stimulation, by both recognition of specific antigen and co-stimuli, T cell memory is formed. Memory T cells retain memory recognition of the initial antigen and pass this specificity on to all T cell progeny formed upon subsequent stimuli. Genetically there is no difference between the naive and memory T cell, yet the memory T cell phenotype is distinct. In light of this, we hypothesize that the macromolecular changes within the T cell that dictates T cell memory is epigenetic in nature. Thus under EMSL's biological interactions theme, focused upon post translational modifications, we propose to identify histone modifications present in memory T cells and determine genes that are regulated by these modified histones. To this end we propose to utilize EMSL's state of the art mass spectrometry facilities and expert team of scientists to resolve the specific histone modifications unique to memory T cells. Following determination of memory T cell histone modifications we will utilize chromatin immunoprecipitation to isolate DNA associated with the modified histones and quantify these genes using massively parallel sequencing (i.e. Illumina). Direct comparison of naive and memory T cells epigenome will shed light upon the molecular determinants of T cell memory, upon which immune cell function and vaccine efficacy rely. The realization of these experiments will have broad significance in both epigenomics and immunobiology, with practical implications toward the improvement of vaccine and immune therapeutics. Project Details
Project type
Large-Scale EMSL Research
Start Date
2009-10-08
End Date
2012-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Lourette NM, HS Smallwood, S Wu, EW Robinson, TC Squier, RD Smith, and L Pasa-Tolic. 2010. "A Top-Down LC-FTICR MS-Based Strategy for Characterizing Oxidized Calmodulin in Activated Macrophages ." Journal of the American Society for Mass Spectrometry 21(6):930-939.