Role of the EHD Family of Endocytic Recycling Regulators for TCR Recycling and T Cell Function

Fany M. Iseka, Benjamin T. Goetz, Insha Mushtaq, Wei An, Luke R. Cypher, Timothy A. Bielecki, Eric C. Tom, Priyanka Arya, Sohinee Bhattacharyya, Matthew D. Storck, Craig L. Semerad, James E. Talmadge, R. Lee Mosley, Vimla Band, Hamid Band

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

T cells use the endocytic pathway for key cell biological functions, including receptor turnover and maintenance of the immuno-logical synapse. Some of the established players include the Rab GTPases, the SNARE complex proteins, and others, which function together with EPS-15 homology domain-containing (EHD) proteins in non-T cell systems. 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-specific TCR transgene. We found that CD4+ T cells from these mice exhibited reduced Ag-driven 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.

Original languageEnglish (US)
Pages (from-to)483-499
Number of pages17
JournalJournal of Immunology
Volume200
Issue number2
DOIs
StatePublished - Jan 15 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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