Requirement of EHD Family of Endocytic Recycling Regulators for T-Cell Functions

Author

Fany M. Iseka, University of Nebraska Medical CenterFollow

Graduation Date

Spring 5-6-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Genetics, Cell Biology & Anatomy

First Advisor

Hamid Band

Abstract

T-cells use the endocytic pathway for key cell biological functions, including receptor turn-over and maintenance of the immunological synapse. Some of the established players include the Rab GTPases, SNARE complex proteins, and others which in non-T-cell systems function together with Eps15 Homology Domain-containing (EHD) proteins. To date, the role of the EHD protein family in T-cell function remains unexplored. We generated conditional EHD1/3/4 knockout mice using CD4-Cre and crossed these with mice bearing a myelin oligodendrocyte glycoprotein (MOG)-specific TCR transgene. We found that CD4⁺ T-cells from these mice exhibited a reduced antigen-driven cell proliferation and IL-2 secretion in vitro. In vivo, these mice exhibited reduced severity of experimental autoimmune encephalomyelitis. Further analyses showed that recycling of the TCR-CD3 complex was impaired, leading to increased lysosomal targeting and reduced surface levels on CD4⁺ T-cells of EHD1/3/4 knockout mice. Our studies reveal a novel role of the EHD family of endocytic recycling regulatory proteins in TCR-mediated T-cell functions.

Recommended Citation

Iseka, Fany M., "Requirement of EHD Family of Endocytic Recycling Regulators for T-Cell Functions" (2017). Theses & Dissertations. 202.
https://digitalcommons.unmc.edu/etd/202