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

Cell reports 2022 Jun 28

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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. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

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. Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function. Cell reports. 2022 Jun 28;39(13):111006