The generation of a specific CD8 T cell immune response following viral infection is critical to host defense. T cell activation, acquisition of effector functions, and differentiation to memory is accompanied by dramatic changes in gene transcription, protein expression and post-translational modifications of proteins. Although post-translational modifications such as phosphorylation have been intensely studied by immunologists, far less attention has been paid to how changes in glycosylation impact T cell functional properties. The importance of the alterations in carbohydrate specificity on T cell glycoproteins and glycolipids is beginning to be explored and evidence suggests that glycosylation plays a key role in immune regulation. To further characterize the changes in glycosylation during memory T cell differentiation, we will perform a systematic examination of differential glycosyltransferase gene expression among T cell populations using a custom-designed microarray which profiles human and mouse transcripts relevant to protein-carbohydrate interactions in cellular communication, the Glycochip. This examination will yield a time-course of a targeted gene expression profile in antigen-specific T cells following viral infection. Importantly, we will systematically characterize and define memory CD8 T cell function in glycosyltransferase-specific gene knockout mice and perform RNAi studies to understand how the loss of these gene products affect hallmark functional traits of memory T cells. These studies may yield important parameters critical to the regulation of the T cell immune response that may have potential for manipulation for therapeutic purposes relevant to vaccination, autoimmunity, and infectious disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Career Transition Award (K22)
Project #
5K22AI057719-02
Application #
7115739
Study Section
Allergy & Clinical Immunology-1 (AITC)
Program Officer
Prograis, Lawrence J
Project Start
2005-09-01
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2008-07-31
Support Year
2
Fiscal Year
2006
Total Cost
$105,462
Indirect Cost
Name
University of Tennessee Knoxville
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
003387891
City
Knoxville
State
TN
Country
United States
Zip Code
37996
Nagarajan, P; Onami, T M; Rajagopalan, S et al. (2009) Role of chromodomain helicase DNA-binding protein 2 in DNA damage response signaling and tumorigenesis. Oncogene 28:1053-62
Zeng, Junwei; Joo, Hye Mee; Rajini, Bheemreddy et al. (2009) The generation of influenza-specific humoral responses is impaired in ST6Gal I-deficient mice. J Immunol 182:4721-7
Suvas, Pratima Krishna; Dech, Heather M; Sambira, Fleurette et al. (2007) Systemic and mucosal infection program protective memory CD8 T cells in the vaginal mucosa. J Immunol 179:8122-7