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

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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.

LanguageEnglish (US)
Pages483-499
Number of pages17
JournalJournal of Immunology
Volume200
Issue number2
DOIs
StatePublished - Jan 15 2018

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Recycling
T-Lymphocytes
Knockout Mice
T-Cell Antigen Receptor-CD3 Complex
rab GTP-Binding Proteins
Myelin-Oligodendrocyte Glycoprotein
SNARE Proteins
Autoimmune Experimental Encephalomyelitis
Transgenes
Synapses
Interleukin-2
Maintenance
Proteins
Protein Domains

ASJC Scopus subject areas

  • Immunology

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Role of the EHD Family of Endocytic Recycling Regulators for TCR Recycling and T Cell Function. / Iseka, Fany M.; Goetz, Benjamin T.; Mushtaq, Insha; An, Wei; Cypher, Luke R.; Bielecki, Timothy A.; Tom, Eric C.; Arya, Priyanka; Bhattacharyya, Sohinee; Storck, Matthew D.; Semerad, Craig L.; Talmadge, James E.; Mosley, R. Lee; Band, Vimla; Band, Hamid.

In: Journal of Immunology, Vol. 200, No. 2, 15.01.2018, p. 483-499.

Research output: Contribution to journalArticle

Iseka, FM, Goetz, BT, Mushtaq, I, An, W, Cypher, LR, Bielecki, TA, Tom, EC, Arya, P, Bhattacharyya, S, Storck, MD, Semerad, CL, Talmadge, JE, Mosley, RL, Band, V & Band, H 2018, 'Role of the EHD Family of Endocytic Recycling Regulators for TCR Recycling and T Cell Function' Journal of Immunology, vol. 200, no. 2, pp. 483-499. https://doi.org/10.4049/jimmunol.1601793
Iseka, Fany M. ; Goetz, Benjamin T. ; Mushtaq, Insha ; An, Wei ; Cypher, Luke R. ; Bielecki, Timothy A. ; Tom, Eric C. ; Arya, Priyanka ; Bhattacharyya, Sohinee ; Storck, Matthew D. ; Semerad, Craig L. ; Talmadge, James E. ; Mosley, R. Lee ; Band, Vimla ; Band, Hamid. / Role of the EHD Family of Endocytic Recycling Regulators for TCR Recycling and T Cell Function. In: Journal of Immunology. 2018 ; Vol. 200, No. 2. pp. 483-499.
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