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ICOS Ligation Recruits the p50{alpha} PI3K Regulatory Subunit to the Immunological Synapse.: ICOS-p50α interactions

Abstract : ICOS ligation in concert with TCR stimulation results in strong PI3K activation in T lymphocytes. The ICOS cytoplasmic tail contains an YMFM motif that binds the p85alpha subunit of class IA PI3K, similar to the YMNM motif of CD28, suggesting a redundant function of the two receptors in PI3K signaling. However, ICOS costimulation shows greater PI3K activity than CD28 in T cells. We show in this report that ICOS expression in activated T cells triggers the participation of p50alpha, one of the regulatory subunits of class IA PI3Ks. Using different T-APC cell conjugate systems, we report that p50alpha accumulates at the immunological synapse in activated but not in resting T cells. Our results demonstrate that ICOS membrane expression is involved in this process and that p50alpha plasma membrane accumulation requires a functional YMFM Src homology 2 domain-binding motif in ICOS. We also show that ICOS triggering with its ligand, ICOSL, induces the recruitment of p50alpha at the synapse of T cell/APC conjugates. In association with the p110 catalytic subunit, p50alpha is known to carry a stronger lipid kinase activity compared with p85alpha. Accordingly, we observed that ICOS engagement results in a stronger activation of PI3K. Together, these findings provide evidence that p50alpha is likely a determining factor in ICOS-mediated PI3K activity in T cells. These results also suggest that a differential recruitment and activity of class IA PI3K subunits represents a novel mechanism in the control of PI3K signaling by costimulatory molecules.
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https://www.hal.inserm.fr/inserm-00282605
Contributor : Jacques Nunès <>
Submitted on : Monday, August 17, 2009 - 10:39:14 AM
Last modification on : Wednesday, June 17, 2020 - 6:16:03 PM
Long-term archiving on: : Friday, May 28, 2010 - 8:24:03 PM

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  • HAL Id : inserm-00282605, version 1
  • PUBMED : 18641334

Citation

Camille Fos, Audrey Salles, Valérie Lang, Florent Carrette, Stéphane Audebert, et al.. ICOS Ligation Recruits the p50{alpha} PI3K Regulatory Subunit to the Immunological Synapse.: ICOS-p50α interactions. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2008, 181 (3), pp.1969-77. ⟨inserm-00282605⟩

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