Langerin

Key takeaways

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

Reference excerpt

Langerin (CD207) is a type II transmembrane protein which is encoded by the CD207 gene in humans. It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of Birbeck granules. Langerin is C-type lectin receptor on Langerhans cells (LCs) and in mice also on dermal interstitial CD103+ dendritic cells (DC) and on resident CD8+ DC in lymph nodes.

Structure Langerin consists of a relatively short intracellular domain and an extracellular domain which consists of a neck-region and a carbohydrate recognition domain (CRD). The intracellular part contains a proline-rich domain (PRD). The neck region consists of alpha-helixes and mediates a formation of langerin homotrimers via a coiled-coil interaction. The homotrimers formation increases avidity and specificity of the antigen. The CRD of langerin is similar to CRDs of other C-type lectins. It contains an EPN motif – a Glu-Pro-Asn rich region. The CRD is divided into two lobes by 2 anti-parallel beta-sheets. The upper lobe creates the primary Ca2+ dependent carbohydrates binding site. In contrast to other lectins, for instance, DC-SIGN / DC-SIGNR and MBP, langerin has only one binding site for Ca2+. In the upper lobe, there have been discovered two other binding sites by a crystallization method. These sites are not dependent on Ca2+ and their relation to the primary binding site is not completely understood. All the binding sites are flanked by positively charged amino acids (K299 and K313) which enable binding of negatively charged sulphated carbohydrates. These amino acids are not present in DC-SIGN.

Function Langerin is expressed in LCs which are located in the epidermis and in vaginal and oral mucosa. LCs are immune cells closely related to macrophages, but by their function, they are more like conventional dendritic cells (cDCs). Langerin recognizes and binds carbohydrates, such as mannose, fucose and N-acetylglucosamine. Thus, LCs may react against pathogens such as HIV-1, Mycobacterium leprae and Candida albicans. After pathogen binding to langerin, fate of the pathogens is not yet understood. It has been proposed that the pathogen is internalised into a cytoplasmatic organelle called Birbeck granule. There, degradation and antigen processing for presentation to T-cells take place. For instance, langerin binds lipoarabinomannans of mycobacteria and inside the Birbeck granules, it contributes to the binding of the antigen to CD1a molecule. In mice, langerin is involved in antigen binding to MHC II glycoproteins and to MHC I glycoproteins during cross-presentation. It seems an intracellular Src homology domain of langerin is important for the formation of Birbeck granules. These organelles contain Rab11a which is a molecule participating in langerin recycling. Langerin has similar function and structure as a DCs surface protein DC-SIGN (CD209). Both receptors bind similar antigens via the CRD, for instance Mycobacterium tuberculosis and HIV-1. However, whereas HIV-1 binding to langerin leads to the elimination of the virus, HIV-1 binding to DC-SIGN leads to infection of the cell.

Clinical significance In human vaginal mucosa, LCs bind the strongly glycosylated glycoprotein gp120 in HIV-1 envelope via langerin. Subsequently, the virus is internalised into the Birbeck granule where it's degraded and processed for presentation. Thus, langerin has an antiviral activity and protects the cell against HIV-1 infection. If langerin is defect or titres of the virus are too high, the HIV-1 infection may happen. Langerin also binds mannose, which is in the outer membrane of fungi, and beta-glucans in membrane folds of fungi. By this way, LCs can protect themselves against pathogens like Candida, Saccharomyces and Malassezia furfur. Furthermore, langerin recognizes Gal-6-sulfated lactosamine of glioblastoma. In the respiratory epithelium, LCs recognize measles virus via langerin and then, they degrade it and present it to CD4+ T-cells.

Polymorphism Single nucleotide polymorphism (SNP) in langerin gene may affect the stability as well as the affinity of the protein for some carbohydrates. The most common polymorphism is a replacement of alanine for valine in the 278. position (rs741326). Allelic frequency of this polymorphism is up to 48%, but it probably does not have any influence on stability and affinity of langerin. Substitution of asparagine for aspartic acid in the 288. position leads to 10-fold reduction in the ability to recognize mannose-BSA. A substitution of tryptophane for arginine in the 264. position leads to a loss of Birbeck granules.

See also Paul Langerhans Langerhans cell

References

Illustrations

Worked examples

Example 1 — a first encounter with Langerin

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

In research: Langerin 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 Langerin 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: Langerin is common in secondary-school and first-year university syllabi. It links to neighbouring topics C-type lectins, Genes on human chromosome 2, Glycobiology, so understanding it makes those chapters shorter.
In everyday life: Look for Langerin 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 Langerin in 20 minutes

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

Frequently asked questions

What is Langerin in simple terms?

Langerin (CD207) is a type II transmembrane protein which is encoded by the CD207 gene in humans. It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of Birbeck granules.

Why does Langerin 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 Langerin?

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 Langerin.