Glycosylation and memory T cell differentiation

University Of Tennessee Knoxville, Knoxville TN

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Abstract

DESCRIPTION (provided by applicant): 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.