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

1 Citations (Scopus)

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

Fingerprint

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

Cite this

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.
@article{dd5b4cfd64134c4a8af7804d38056a90,
title = "Role of the EHD Family of Endocytic Recycling Regulators for TCR Recycling and T Cell Function",
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.",
author = "Iseka, {Fany M.} and Goetz, {Benjamin T.} and Insha Mushtaq and Wei An and Cypher, {Luke R.} and Bielecki, {Timothy A.} and Tom, {Eric C.} and Priyanka Arya and Sohinee Bhattacharyya and Storck, {Matthew D.} and Semerad, {Craig L} and Talmadge, {James E} and Mosley, {R Lee} and Vimla Band and Hamid Band",
year = "2018",
month = "1",
day = "15",
doi = "10.4049/jimmunol.1601793",
language = "English (US)",
volume = "200",
pages = "483--499",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Role of the EHD Family of Endocytic Recycling Regulators for TCR Recycling and T Cell Function

AU - Iseka, Fany M.

AU - Goetz, Benjamin T.

AU - Mushtaq, Insha

AU - An, Wei

AU - Cypher, Luke R.

AU - Bielecki, Timothy A.

AU - Tom, Eric C.

AU - Arya, Priyanka

AU - Bhattacharyya, Sohinee

AU - Storck, Matthew D.

AU - Semerad, Craig L

AU - Talmadge, James E

AU - Mosley, R Lee

AU - Band, Vimla

AU - Band, Hamid

PY - 2018/1/15

Y1 - 2018/1/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85044784318&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044784318&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1601793

DO - 10.4049/jimmunol.1601793

M3 - Article

VL - 200

SP - 483

EP - 499

JO - Journal of Immunology

T2 - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -