Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function

Vera Marie E. Dunlock; Abbey B. Arp; Simar Pal Singh; Stéphanie Charrin; Viet Nguyen; Erik Jansen; Fleur Schaper; Martin Ter Beest; Malou Zuidscherwoude; Sjoerd J. van Deventer; Britt Nakken; Peter Szodoray; Maria C. Demaria; Mark D. Wright; Laia Querol Cano; Eric Rubinstein; Annemiek B. van Spriel

doi:10.1016/j.celrep.2022.111006

Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function

Vera Marie E. Dunlock, Abbey B. Arp, Simar Pal Singh, Stéphanie Charrin, Viet Nguyen, Erik Jansen, Fleur Schaper, Martin Ter Beest, Malou Zuidscherwoude, Sjoerd J. van Deventer, Britt Nakken, Peter Szodoray, Maria C. Demaria, Mark D. Wright, Laia Querol Cano, Eric Rubinstein, Annemiek B. van Spriel

Immunology Alfred Hospital

Research output: Contribution to journal › Article › Research › peer-review

16 Citations (Scopus)

Abstract

T cells depend on the phosphatase CD45 to initiate T cell receptor signaling. Although the critical role of CD45 in T cells is established, the mechanisms controlling function and localization in the membrane are not well understood. Moreover, the regulation of specific CD45 isoforms in T cell signaling remains unresolved. By using unbiased mass spectrometry, we identify the tetraspanin CD53 as a partner of CD45 and show that CD53 controls CD45 function and T cell activation. CD53-negative T cells (Cd53^−/−) exhibit substantial proliferation defects, and Cd53^−/− mice show impaired tumor rejection and reduced IFNγ-producing T cells compared with wild-type mice. Investigation into the mechanism reveals that CD53 is required for CD45RO expression and mobility. In addition, CD53 is shown to stabilize CD45 on the membrane and is required for optimal phosphatase activity and subsequent Lck activation. Together, our findings reveal CD53 as a regulator of CD45 activity required for T cell immunity.

Original language	English
Article number	111006
Number of pages	27
Journal	Cell Reports
Volume	39
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2022.111006
Publication status	Published - 28 Jun 2022

Keywords

CD45
CD53
CP: Immunology
nanodomain
phosphatase
plasma membrane
signaling
T cells
TCR
tetraspanin

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10.1016/j.celrep.2022.111006Licence: CC BY

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Dunlock, V. M. E., Arp, A. B., Singh, S. P., Charrin, S., Nguyen, V., Jansen, E., Schaper, F., Beest, M. T., Zuidscherwoude, M., van Deventer, S. J., Nakken, B., Szodoray, P., Demaria, M. C., Wright, M. D., Querol Cano, L., Rubinstein, E., & van Spriel, A. B. (2022). Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function. Cell Reports, 39(13), Article 111006. https://doi.org/10.1016/j.celrep.2022.111006

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title = "Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function",

abstract = "T cells depend on the phosphatase CD45 to initiate T cell receptor signaling. Although the critical role of CD45 in T cells is established, the mechanisms controlling function and localization in the membrane are not well understood. Moreover, the regulation of specific CD45 isoforms in T cell signaling remains unresolved. By using unbiased mass spectrometry, we identify the tetraspanin CD53 as a partner of CD45 and show that CD53 controls CD45 function and T cell activation. CD53-negative T cells (Cd53−/−) exhibit substantial proliferation defects, and Cd53−/− mice show impaired tumor rejection and reduced IFNγ-producing T cells compared with wild-type mice. Investigation into the mechanism reveals that CD53 is required for CD45RO expression and mobility. In addition, CD53 is shown to stabilize CD45 on the membrane and is required for optimal phosphatase activity and subsequent Lck activation. Together, our findings reveal CD53 as a regulator of CD45 activity required for T cell immunity.",

keywords = "CD45, CD53, CP: Immunology, nanodomain, phosphatase, plasma membrane, signaling, T cells, TCR, tetraspanin",

author = "Dunlock, {Vera Marie E.} and Arp, {Abbey B.} and Singh, {Simar Pal} and St{\'e}phanie Charrin and Viet Nguyen and Erik Jansen and Fleur Schaper and Beest, {Martin Ter} and Malou Zuidscherwoude and {van Deventer}, {Sjoerd J.} and Britt Nakken and Peter Szodoray and Demaria, {Maria C.} and Wright, {Mark D.} and {Querol Cano}, Laia and Eric Rubinstein and {van Spriel}, {Annemiek B.}",

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year = "2022",

month = jun,

day = "28",

doi = "10.1016/j.celrep.2022.111006",

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Dunlock, VME, Arp, AB, Singh, SP, Charrin, S, Nguyen, V, Jansen, E, Schaper, F, Beest, MT, Zuidscherwoude, M, van Deventer, SJ, Nakken, B, Szodoray, P, Demaria, MC , Wright, MD, Querol Cano, L, Rubinstein, E & van Spriel, AB 2022, 'Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function', Cell Reports, vol. 39, no. 13, 111006. https://doi.org/10.1016/j.celrep.2022.111006

TY - JOUR

T1 - Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function

AU - Dunlock, Vera Marie E.

AU - Arp, Abbey B.

AU - Singh, Simar Pal

AU - Charrin, Stéphanie

AU - Nguyen, Viet

AU - Jansen, Erik

AU - Schaper, Fleur

AU - Beest, Martin Ter

AU - Zuidscherwoude, Malou

AU - van Deventer, Sjoerd J.

AU - Nakken, Britt

AU - Szodoray, Peter

AU - Demaria, Maria C.

AU - Wright, Mark D.

AU - Querol Cano, Laia

AU - Rubinstein, Eric

AU - van Spriel, Annemiek B.

PY - 2022/6/28

Y1 - 2022/6/28

N2 - T cells depend on the phosphatase CD45 to initiate T cell receptor signaling. Although the critical role of CD45 in T cells is established, the mechanisms controlling function and localization in the membrane are not well understood. Moreover, the regulation of specific CD45 isoforms in T cell signaling remains unresolved. By using unbiased mass spectrometry, we identify the tetraspanin CD53 as a partner of CD45 and show that CD53 controls CD45 function and T cell activation. CD53-negative T cells (Cd53−/−) exhibit substantial proliferation defects, and Cd53−/− mice show impaired tumor rejection and reduced IFNγ-producing T cells compared with wild-type mice. Investigation into the mechanism reveals that CD53 is required for CD45RO expression and mobility. In addition, CD53 is shown to stabilize CD45 on the membrane and is required for optimal phosphatase activity and subsequent Lck activation. Together, our findings reveal CD53 as a regulator of CD45 activity required for T cell immunity.

AB - T cells depend on the phosphatase CD45 to initiate T cell receptor signaling. Although the critical role of CD45 in T cells is established, the mechanisms controlling function and localization in the membrane are not well understood. Moreover, the regulation of specific CD45 isoforms in T cell signaling remains unresolved. By using unbiased mass spectrometry, we identify the tetraspanin CD53 as a partner of CD45 and show that CD53 controls CD45 function and T cell activation. CD53-negative T cells (Cd53−/−) exhibit substantial proliferation defects, and Cd53−/− mice show impaired tumor rejection and reduced IFNγ-producing T cells compared with wild-type mice. Investigation into the mechanism reveals that CD53 is required for CD45RO expression and mobility. In addition, CD53 is shown to stabilize CD45 on the membrane and is required for optimal phosphatase activity and subsequent Lck activation. Together, our findings reveal CD53 as a regulator of CD45 activity required for T cell immunity.

KW - CD45

KW - CD53

KW - CP: Immunology

KW - nanodomain

KW - phosphatase

KW - plasma membrane

KW - signaling

KW - T cells

KW - TCR

KW - tetraspanin

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U2 - 10.1016/j.celrep.2022.111006

DO - 10.1016/j.celrep.2022.111006

M3 - Article

C2 - 35767951

AN - SCOPUS:85133147870

SN - 2211-1247

VL - 39

JO - Cell Reports

JF - Cell Reports

IS - 13

M1 - 111006

ER -

Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function

Abstract

Keywords

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