Co-inhibition by PD-1

Stable Identifier
R-HSA-389948
Type
Pathway
Species
Homo sapiens
Compartment
Synonyms
PD-1 signaling
ReviewStatus
5/5
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Programmed cell death protein 1 (PD-1) is a crucial inhibitory receptor that regulates T cell receptor (TCR) signaling and plays a vital role in maintaining immune homeostasis. PD-1 exerts its suppressive effects both directly, by inhibiting early activation events that are otherwise enhanced by co-stimulatory signals like CD28, and indirectly, by reducing interleukin-2 (IL-2) production, which is essential for T cell proliferation and survival. Upon ligation, PD-1 inhibits the expression of key survival and differentiation factors, such as Bcl-xL, and downregulates transcription factors that are central to effector T cell function, including GATA-3, T-bet, and Eomes. Mechanistically, PD-1 recruits the tyrosine phosphatases SHP-1 and SHP-2 to the immune synapse, leading to the dephosphorylation of critical signaling molecules like the CD3-zeta chain, PI3K, and AKT, thereby attenuating TCR signaling and inhibiting T cell activation and function (Keir et al. 2008).
Literature References
PubMed ID Title Journal Year
18759926 Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways

Fife, BT, Bluestone, JA

Immunol Rev 2008
18173375 PD-1 and its ligands in tolerance and immunity

Keir, ME, Sharpe, AH, Freeman, GJ, Butte, MJ

Annu Rev Immunol 2008
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Orthologous Events
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BioModels Database
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