biology

TNFRSF4

TNFRSF4 is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand TNFRSF4 rather than just read about it. In short: Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cel…

Key takeaways

TNFRSF4 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect TNFRSF4 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of TNFRSF4 from memory before moving on to harder problems.

Reference excerpt

Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell; without CD28, expression of OX40 is delayed and of fourfold lower levels.

Function OX40 has no effect on the proliferative abilities of CD4+ cells for the first three days, however after this time proliferation begins to slow and cells die at a greater rate, due to an inability to maintain a high level of PKB activity and expression of Bcl-2, Bcl-XL and survivin. OX40L binds to OX40 receptors on T-cells, preventing them from dying and subsequently increasing cytokine production. OX40 has a critical role in the maintenance of an immune response beyond the first few days and onwards to a memory response due to its ability to enhance survival. OX40 also plays a crucial role in both Th1 and Th2 mediated reactions in vivo. OX40 binds TRAF2, 3 and 5 as well as PI3K by an unknown mechanism. TRAF2 is required for survival via NF-κB and memory cell generation whereas TRAF5 seems to have a more negative or modulatory role, as knockouts have higher levels of cytokines and are more susceptible to Th2-mediated inflammation. TRAF3 may play a critical role in OX40-mediated signal transduction. CTLA-4 is down-regulated following OX40 engagement in vivo and the OX40-specific TRAF3 DN defect was partially overcome by CTLA-4 blockade in vivo. TRAF3 may be linked to OX40-mediated memory T cell expansion and survival, and point to the down-regulation of CTLA-4 as a possible control element to enhance early T cell expansion through OX40 signaling.

Clinical significance OX40 has been implicated in the pathologic cytokine storm associated with certain viral infections, including the H5N1 bird flu.

As a drug or drug target An artificially created biologic fusion protein, OX40-immunoglobulin (OX40-Ig), prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response. Experiments in mice have demonstrated that OX40-Ig can reduce the symptoms associated with the cytokine storm (an immune overreaction) while allowing the immune system to fight off the virus successfully. An anti-OX40 antibody GSK3174998 has started clinical trials as a cancer treatment. Research in mice has included the combination of an agonistic OX40 antibody (clone OX86) injected directly into a tumor in combination with an unmethylated CpG oligonucleotide, which as a TLR9 ligand activates expression of OX40 so that it can be affected.

Interactions CD134 has been shown to interact with TRAF5 and TRAF2.

References

External links Human TNFRSF4 genome location and TNFRSF4 gene details page in the UCSC Genome Browser.

Illustrations

Worked examples

Example 1 — a first encounter with TNFRSF4

Start with the simplest possible case. Write down what TNFRSF4 claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to TNFRSF4 before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about TNFRSF4 ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of TNFRSF4

In research: TNFRSF4 appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses TNFRSF4 in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: TNFRSF4 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Clusters of differentiation, Genes on human chromosome 1, T cells, so understanding it makes those chapters shorter.
In everyday life: Look for TNFRSF4 outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study TNFRSF4 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what TNFRSF4 means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain TNFRSF4 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is TNFRSF4 in simple terms?

Why does TNFRSF4 matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study TNFRSF4?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on TNFRSF4.