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 journalArticle

2 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
Publication statusPublished - Jan 15 2018

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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