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

  • Cell Rep. 2022 Jun 28;39(13):111006. doi: 10.1016/j.celrep.2022.111006.
Vera-Marie E Dunlock  1 ,  Abbey B Arp  1 ,  Simar Pal Singh  1 ,  Stéphanie Charrin  2 ,  Viet Nguyen  3 ,  Erik Jansen  1 ,  Fleur Schaper  1 ,  Martin Ter Beest  1 ,  Malou Zuidscherwoude  1 ,  Sjoerd J van Deventer  1 ,  Britt Nakken  4 ,  Peter Szodoray  4 ,  Maria C Demaria  5 ,  Mark D Wright  5 ,  Laia Querol Cano  1 ,  Eric Rubinstein  2 ,  Annemiek B van Spriel  6
Affiliations
  • 1. Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
  • 2. Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, 75013 Paris, France.
  • 3. Université Paris-Saclay, INSERM, UMS33, 94800 Villejuif, France.
  • 4. Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, NO-0424 Oslo, Norway; K.G. Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • 5. Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.
  • 6. Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands. Electronic address: [email protected].
PMID: 35767951 DOI: 10.1016/j.celrep.2022.111006
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; T cells; TCR; nanodomain; phosphatase; plasma membrane; signaling; tetraspanin.