IL2RA

Key takeaways

IL2RA belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect IL2RA to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of IL2RA from memory before moving on to harder problems.

Reference excerpt

The interleukin-2 receptor alpha chain (also called Tac antigen, P55, and mainly CD25) is a protein involved in the assembly of the high-affinity interleukin-2 receptor, consisting of alpha (IL2RA), beta (IL2RB) and the common gamma chain (IL2RG). As the name indicates, this receptor interacts with interleukin-2, a pleiotropic cytokine which plays an important role in immune homeostasis.

Genetics The human protein interleukin-2 receptor subunit alpha is encoded by a gene called IL2RA with a length around 51,6 kb. Alternative names for this protein coding gene are IL2R, IDDM10 and TCGFR. Location of IL2RA in human genome is on the short arm of 10th chromosome (10p15.1). Several frequent point mutations, single nucleotide polymorphism (SNP), have been identified in or in close proximity to IL2RA gene in the population. These SNPs have been linked mainly to susceptibility to immune dysregulation disorders, with majority found in research on multiple sclerosis (MS) and type 1 diabetes mellitus. IL2RA gene orthologues with identical protein functionality are relatively abundant and constant among animal species, especially in mammals subgroups. Moreover, conserved homologs of this gene are in mouse, rat, dog, cow, chimpanzee and Rhesus monkey.

Expression CD25 is expressed broadly among leukocytes. The highest surface expression of this protein is on regulatory T cells (Tregs), where CD25 is expressed constitutively, especially on a subset classified as naturally occurring Tregs. It can also be found on activated B cells, NK (natural killer) cells, thymocytes, and some myeloid lineage cells (e.g. macrophages, dendritic cells). IL2RA has been used as a marker to identify CD4+FoxP3+ regulatory T cells in mice. However, there are species differences as CD25 is constitutively expressed by a large proportion of resting memory T cells non-regulatory CD4 T cells in humans that are absent in mice. High expression of CD25 is also found on TCR activated conventional T cells (both CD8+ and CD4+ T lymphocytes), where it is considered to be a marker of T cell activation. Additionally, expression of the IL-2 receptor alpha subunit can be found in non-lymphoid tissues such as lungs (alveolar macrophages), liver (Kupffer cells) and skin (Langerhans cells). IL2RA protein can be expressed in many types of neoplastic cells, such as in most B-cell neoplasms, T-cell lymphomas, some acute nonlymphocytic leukemias, neuroblastomas, mastocytosis, Waldenstrom macroglobuliaemia and tumor infiltrating lymphocytes.

Structure Interleukin-2 receptor alpha chain is an integral-membrane protein, more precisely type I transmembrane protein. This bitopic polypeptide is constructed by a sequence of 272 amino acids and has a molecular mass of around 30.8 kDa. CD25 consists of three domains: extracellular (N-terminus), transmembrane (alpha-helix) and cytoplasmic (C-terminus). However, while extracellular part is able to function as a binding site for interleukin-2, short cytoplasmic domain lacks an ability to induce intracellular signalling and therefore needs to oligomerise with other IL-2 receptor subunits. The interleukin-2 (IL2) receptor alpha (IL2RA) and beta (IL2RB) chains, together with the common gamma chain (IL2RG), constitute the high-affinity IL-2 receptor complex (Kd ~10−11M). Homodimeric alpha chains (IL2RA) result in low-affinity receptor (Kd ~10−8M) with no signalling ability, while dimeric beta (IL2RB) and gamma chains (IL2RG) produce a medium-affinity receptor (Kd ~10−9M). Moreover, CD25 is an exclusive subunit that entirely binds IL-2, while CD132 binds the shared γc family cytokines (IL-4, IL-7, IL-9, IL-15 and IL-21), and the CD122 subunit binds also IL-15. Soluble IL2RA has been isolated and determined to result from extracellular proteolysis during activation of T lymphocytes. Also, alternately-spliced IL2RA mRNAs have been isolated, but the significance of each is currently unknown.

Signalling cascade of interleukin-2 receptor Interleukin-2 can interact with intermediate-affinity dimeric IL-2 receptor, which consists of beta (CD122) and gamma (CD132) chains, or with high-affinity trimeric complex, where the addition of an alpha subunit (CD25) constructs the IL-2 receptor and provides enhanced specific binding force. After activation of the receptor by its ligand, heterodimerisation of beta and gamma intracellular domains takes place. This coupling of subunits brings together Janus kinases JAK1 and JAK3, considering their association with respective cytoplasmic parts of beta and gamma subunits. Downstream phosphorylation leads to initiation of three signalling pathways: JAK-STAT pathway, PI3K/Akt/mTOR pathway and Ras/Raf/MEK/ERK (MAPK) pathway. Regarding JAK-STAT pathway, particular signal transducers and activators of transcription participate in this signalling cascade, namely STAT5, STAT1 and STAT3. After dimerisation, they translocate to nucleus to perform transcription factor functions. All three signalling pathways are important for diverse cellular regulations, in terms of increased survival (anti-apoptotic effect), proliferation and cell growth, transcriptional regulation and cell differentiation. T lymphocytes are influenced by IL-2R signalling in case of CD4+ T helper subtype differentiation: promoting Th1, Th2, Th9, Tfr (T follicular regulatory cells) and suppressing Th17, Tfh ( T follicular helper cells). Additionally, strength of IL-2R signalling in CD8+ T cytotoxic lymphocytes may be connected to phenotypic fate of these cells for effector and memory T cells formation.

Clinical significance Roifman's group was the first to identify immunological consequences of CD25 loss and the patient has suffered from chronic infections and severe autoimmunity resembling Immune dysregulation, Polyendocrinopathy, Enteropathy X-linked (IPEX) syndrome, caused by mutations in FOXP3 gene.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with IL2RA

Start with the simplest possible case. Write down what IL2RA 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 IL2RA 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 IL2RA 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 IL2RA

In research: IL2RA 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 IL2RA 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: IL2RA is common in secondary-school and first-year university syllabi. It links to neighbouring topics Clusters of differentiation, Genes on human chromosome 10, so understanding it makes those chapters shorter.
In everyday life: Look for IL2RA 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.

How to study IL2RA in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what IL2RA 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 IL2RA out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is IL2RA in simple terms?

The interleukin-2 receptor alpha chain (also called Tac antigen, P55, and mainly CD25) is a protein involved in the assembly of the high-affinity interleukin-2 receptor, consisting of alpha (IL2RA), beta (IL2RB) and the common gamma chain (IL2RG). As the name indicates, this receptor interacts with…

Why does IL2RA 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 IL2RA?

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 IL2RA.