CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms

By R. Parry, J. Chemnitz, Kenneth A. Frauwirth, A. Lanfranco, Inbal Braunstein, Sumire V. Kobayashi, Peter S. Linsley, Craig B. Thompson, J. Riley. Molecular and Cellular Biology, 2004

1,879 citations recorded by the source corpus.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/4747959d51bce9e7241a5c9270d2c3174cb9d79f

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In Immunology

Citations in the corpus

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022, background): “On the other hand, CTLA-4 engagement with CD80/CD86 counteracts TCR-induced downstream signaling and suppresses PI3K-Akt pathway (vital signaling of T cell activation), via SHP-2 and protein phosphatase 2A (PP2A) [123, 124].”
Overcoming T cell exhaustion in infection and cancer (2015, background): “PD-1 can: (A) antagonize TCR signaling by recruiting phosphatases [107– 110], (B) modulate the PI3K/AKT/mTOR pathway, implicating PD-1 in metabolism, nutrient sensing, survival, and cell growth [104, 111, 112], (C) modulate the Ras pathway, linking PD-1 to cell cycle [112], (D) induce expression of ”
Interactions between programmed death-1 and programmed death ligand-1 promote tolerance by blocking the T cell receptor-induced stop signal (2009, background): “In addition, PD-1 may directly recruit phosphatases such as SHP-1 and SHP-2, which interfere with TCR signalin”
PD-1– and CTLA-4–Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses (2013, background): “In vitro ligation of CTLA-4 or PD-1 during T cell stimulation blocks activation, cytokine release, and proliferation (26).”
Immune checkpoint blockade: a common denominator approach to cancer therapy (2015, background): “PD-1: Similarities to and Differences from CTLA-4 The PD-1 system of immune modulation bears similarities to CTLA-4 as well as key distinctions (Parry et al., 2005).”
CTLA-4 and PD-1 Pathways (2016, background): “If a T cell experiences coincident TCR and PD-1 binding, PD-1-generated signals prevent phosphorylation of key TCR signaling intermediates, which terminates early TCR signaling and reduces activation of T cells.(10,21) PD-1 expression is a hallmark of “exhausted” T cells that have experienced high l”
T cell exhaustion (2011, background): “Both PD-1 and CTLA-4 can inhibit signaling by the serine-threonine kinase Akt but seem to do so by different molecular mechanism”
Bioenergetic insufficiencies due to metabolic alterations regulated by PD-1 are an early driver of CD8+ T cell exhaustion (2016, background): “The intracellular tail of PD-1 contains an immunotyrosine inhibitorymotif (ITIM) and an immunotyrosine switchmotif (ITSM), that can recruit phosphatases such as SHP-2, allowing dephosphorylation of key signal transducers (Chemnitz et al., 2004; Okazaki et al., 2001).”
Metabolic Regulation of Immune Responses (2014, background): “Ligation of the inhibitory receptors PD-1 and CTLA-4, which inhibit T cell activation, prevented PI3K/Akt activation and the switch to glycolytic metabolism (91, 94, 95).”
The PD-1 Pathway in Tolerance and Autoimmunity (2010, background): “Importantly, the cell survival gene Bcl-xL was upregulated following ligation of CTLA-4 but not PD-1, suggesting a means by which PD-1 engagement could make T cells more susceptible to apoptosis.”
Control of peripheral T‐cell tolerance and autoimmunity via the CTLA‐4 and PD‐1 pathways (2008, background): “Distinct from PD-1, CTLA-4 has also been shown to interact with PP2a, suggesting an additional inhibitory pathway (75).”
Metabolic competition in the tumor microenvironment is a driver of cancer progression (2015, background): “, 2013), and glucose uptake (Parry et al., 2005), but the exact mechanisms of how these various treatments work remain unclear (Page et al.”