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

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Iseka, Fany M.
Endocytic Traffic; Recycling; Endosomes; EHD proteins; T-cells; TCRs; Other Immunology and Infectious Disease
thesis / dissertation description
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.