OX40L binds OX40

Stable Identifier
R-HSA-5692315
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

T-cell activation is mediated not only by antigen stimulation through T-cell receptors but also by costimulatory signals through costimulatory molecules. Among several costimulatory molecules, the tumor necrosis factor (TNF) receptor family member OX40 (also known as TNFRSF4 or CD134) plays a key role in the survival and homeostasis of effector and memory T cells (Godfrey et al. 1994, Kashiwakura et al. 2004, Zingoni et al. 2004). OX40 mediates this costimulation by binding to its partner OX40L (also known as TNFSF4 or CD252). OX40 is a type I transmembrane protein expressed predominantly on T-lymphocytes early after antigen activation. It binds with OX40L trimer expressed on activated antigen presenting cells and endothelial cells within acute inflammatory environments. OX40 mediates signalling independently and also can augment antigen-driven TCR signalling. OX40 signalling leads to the activation of NFkB1 (p50-RELA) to stimulate survival signals to T cells in the absence of antigen recognition. It can also activate hence to activation of noncanonical NF-κB2 (p52-RELB) through NIK which might also be necessary for transmitting survival signals (Kawamata et al. 1998, Arch et al. 1998). OX40 can also enhance TCR-induced calcium influx, leading to strong nuclear accumulation of NFATc1 and NFATc2 that likely regulate production of cytokines (So et al. 2006, Croft 2010).

Literature References
PubMed ID Title Journal Year
20510730 OX40-OX40 ligand interaction in T-cell-mediated immunity and immunopathology

Ishii, N, Takahashi, T, Soroosh, P, Sugamura, K

Adv. Immunol. 2010
15356117 Cross-talk between activated human NK cells and CD4+ T cells via OX40-OX40 ligand interactions

Zingoni, A, Sornasse, T, Cocks, BG, Tanaka, Y, Santoni, A, Lanier, LL

J. Immunol. 2004
15470070 T cell proliferation by direct cross-talk between OX40 ligand on human mast cells and OX40 on human T cells: comparison of gene expression profiles between human tonsillar and lung-cultured mast cells

Kashiwakura, J, Yokoi, H, Saito, H, Okayama, Y

J. Immunol. 2004
16501042 Signals from OX40 regulate nuclear factor of activated T cells c1 and T cell helper 2 lineage commitment

So, T, Song, J, Sugie, K, Altman, A, Croft, M

Proc. Natl. Acad. Sci. U.S.A. 2006
7913952 Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor

Godfrey, WR, Fagnoni, FF, Harara, MA, Buck, D, Engleman, EG

J. Exp. Med. 1994
20307208 Control of immunity by the TNFR-related molecule OX40 (CD134)

Croft, M

Annu. Rev. Immunol. 2010
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