Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2

By T. Yokosuka, M. Takamatsu, Wakana Kobayashi-Imanishi, A. Hashimoto-Tane, M. Azuma, T. Saito. Journal of Experimental Medicine, 2012

1,074 citations recorded by the source corpus.

After encounter with its ligand, PD-1 translocates into TCR microclusters, where it transiently recruits SHP2 and suppresses phosphorylation of TCR signaling components and TCR-driven stop signals.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/8d173be4e436e974d557f874afa4946e96bdb1d5

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Citations in the corpus

Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory (2019, background): “It binds the PD-1 receptor on immune T cells, leading to Sh2p-driven dephosphorylation of the T cell receptor and its co-receptor CD28, thereby suppressing antigen-driven activation of T cells (Hui et al., 2017; Yokosuka et al., 2012).”
T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition (2016, background): “2B), but not Shp1, Csk, SHIP-1, or other SH2 proteins tested.”
Bioenergetic insufficiencies due to metabolic alterations regulated by PD-1 are an early driver of CD8+ T cell exhaustion (2016, background): “Engagement of PD-1 by its ligand PD-L1 results 358 Immunity 45, 358–373, August 16, 2016 ª 2016 Elsevier Inc. in the formation of microclusters with the TCR (Yokosuka et al., 2012) and PD-1 inhibits proximal signaling molecules after TCR engagement (Sheppard et al., 2004).”
CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer. (2019, background): “PD-1 recruitment of SHP-2 has also been recently implicated in the dephosphorylation of CD28 as a major mechanism through which PD-1 promotes T cell exhaustion (110, 219).”
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022, background): “Subsequently, Src homology region 2 domain-containing phosphatase (SHP-2) is recruited and activated, reversing the phosphorylation of downstream signaling of TCR and CD28 [3, 4].”
PD-1– and CTLA-4–Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses (2013, result): “Exposure to CD19 target AAPCs showed lower SHP-1 and SHP-2 phosphorylation levels compared to the basal levels seen after exposure to AAPCs lacking CD19, consistent with previous studies demonstrating dephosphorylation and consequent blockade of the suppressive effects of SHP-1/2 uponT cell activati”