描述：
OX40 (CD134; TNFRSF4) is a T cell costimulatory molecule of the TNF receptor superfamily
that coordinates with other membranebound costimulators such as CD28, CD40, CD30,
CD27 and 41BB.OX40 is expressed on naïve CD4+ T cells only after engagement of the TCR
by antigen presenting cells (APC; dendritic and B cells), and costimulation by CD40/CD40
ligand and CD28/B7. It is maximal at 2-5 days post activation, or 4 hours post reactivation
of memory T cells. Human OX40 is a 48 kDa type I transmembrane glycoprotein with a 28
amino acid (aa) signal sequence, a 185 aa extracellular domain (ECD) that has four TNFRCys
repeats and an Oglycosylated hinge region, a 20 aa transmembrane segment, and a 41 aa
cytoplasmic domain. The ECD of human OX40 shows 71%, 68%, 67%, 64% and 64% aa identity
with feline, canine, rabbit, mouse and rat OX40 ECD, respectively. Engagement of OX40 on
activated CD4+ T cells by OX40 ligand on activated dendritic cells promotes T cell survival and
proliferation, prolongs the immune response, and enhances the number of cells making the
transition from effector to memory T cells.OX40 signal transduction includes binding TNF
receptorassociated factors (TRAFs), and activating NFκB and PI3 kinase to enhance
expression of cytokines, antiapoptotic Bcl2 family members, survivin and the chemokine
receptor CXCR5. CXCR5 promotes T cell migration to germinal centers to deliver B cell help.
Studies using knockout or transgenic mice, and agonistic or blocking antibodies, show that
OX40/OX40L interaction is critical for establishing or reactivating memory T cells and breaking
immune tolerance. Blockade of OX40 engagement is efficacious in animal models of allergic
airway inflammation, graftversushost disease and autoimmune disease.
原厂资料：
OX40 (CD134; TNFRSF4) is a T cell costimulatory molecule of the TNF receptor superfamily
that coordinates with other membranebound costimulators such as CD28, CD40, CD30,
CD27 and 41BB.OX40 is expressed on naïve CD4+ T cells only after engagement of the TCR
by antigen presenting cells (APC; dendritic and B cells), and costimulation by CD40/CD40
ligand and CD28/B7. It is maximal at 2-5 days post activation, or 4 hours post reactivation
of memory T cells. Human OX40 is a 48 kDa type I transmembrane glycoprotein with a 28
amino acid (aa) signal sequence, a 185 aa extracellular domain (ECD) that has four TNFRCys
repeats and an Oglycosylated hinge region, a 20 aa transmembrane segment, and a 41 aa
cytoplasmic domain. The ECD of human OX40 shows 71%, 68%, 67%, 64% and 64% aa identity
with feline, canine, rabbit, mouse and rat OX40 ECD, respectively. Engagement of OX40 on
activated CD4+ T cells by OX40 ligand on activated dendritic cells promotes T cell survival and
proliferation, prolongs the immune response, and enhances the number of cells making the
transition from effector to memory T cells.OX40 signal transduction includes binding TNF
receptorassociated factors (TRAFs), and activating NFκB and PI3 kinase to enhance
expression of cytokines, antiapoptotic Bcl2 family members, survivin and the chemokine
receptor CXCR5. CXCR5 promotes T cell migration to germinal centers to deliver B cell help.
Studies using knockout or transgenic mice, and agonistic or blocking antibodies, show that
OX40/OX40L interaction is critical for establishing or reactivating memory T cells and breaking
immune tolerance. Blockade of OX40 engagement is efficacious in animal models of allergic
airway inflammation, graftversushost disease and autoimmune disease.
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