CD207
   HOME

TheInfoList



OR:

Langerin (CD207) is a type II
transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...
which is encoded by the ''CD207''
gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
in humans. It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of
Birbeck granules Birbeck granules, also known as Birbeck bodies, are rod shaped or "tennis-racket" cytoplasmic organelles with a central linear density and a striated appearance. First described in 1961 (where they were simply termed "characteristic granules"), the ...
. Langerin is
C-type lectin A C-type lectin (CLEC) is a type of carbohydrate-binding protein known as a lectin. The C-type designation is from their requirement for calcium for binding. Proteins that contain C-type lectin domains have a diverse range of functions including c ...
receptor on
Langerhans cells A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in t ...
(LCs) and in mice also on dermal interstitial CD103+
dendritic cells Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...
(DC) and on resident CD8+ DC in
lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
.


Structure

Langerin consists of a relatively short intracellular domain and an extracellular domain which consists of a neck-region and a
carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or m ...
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 In biochemistry, avidity refers to the accumulated strength of ''multiple'' affinities of individual non-covalent binding interactions, such as between a protein receptor and its ligand, and is commonly referred to as functional affinity. Avidity di ...
and specificity of the
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
. 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-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) also known as CD209 ( Cluster of Differentiation 209) is a protein which in humans is encoded by the ''CD209'' gene. DC-SIGN is a C-type lectin receptor pr ...
/ 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 The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed '' lamina propria''. The oral cavity has sometimes been des ...
. LCs are
immune cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
closely related to
macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
, but by their function, they are more like conventional dendritic cells (cDCs). Langerin recognizes and binds carbohydrates, such as
mannose Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...
,
fucose Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) li ...
and N-acetylglucosamine. Thus, LCs may react against
pathogens In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...
such as
HIV-1 The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
,
Mycobacterium leprae ''Mycobacterium leprae'' (also known as the leprosy bacillus or Hansen's bacillus), is one of the two species of bacteria that cause Hansen’s disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves an ...
and
Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...
. 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 A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
take place. For instance, langerin binds lipoarabinomannans of mycobacteria and inside the Birbeck granules, it contributes to the binding of the antigen to
CD1a #REDIRECT CD1A {{R from different capitalization ...
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 Ras-related protein Rab-11A is a protein that in humans is encoded by the ''RAB11A'' gene. Function The protein encoded by this gene belongs to the small GTPase superfamily, Rab family. It is associated with both constitutive and regulated secr ...
which is a molecule participating in langerin recycling. Langerin has similar function and structure as a DCs surface protein
DC-SIGN DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) also known as CD209 ( Cluster of Differentiation 209) is a protein which in humans is encoded by the ''CD209'' gene. DC-SIGN is a C-type lectin receptor pr ...
(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 Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
.


Clinical significance

In human vaginal mucosa, LCs bind the strongly glycosylated glycoprotein
gp120 Envelope glycoprotein GP120 (or gp120) is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1988. The 120 in its name comes from ...
in
HIV-1 The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
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 Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...
, which is in the outer membrane of
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
, and beta-glucans in membrane folds of fungi. By this way, LCs can protect themselves against pathogens like '' Candida'', ''
Saccharomyces ''Saccharomyces'' is a genus of fungi that includes many species of yeasts. ''Saccharomyces'' is from Greek σάκχαρον (sugar) and μύκης (fungus) and means ''sugar fungus''. Many members of this genus are considered very important in f ...
'' and '' Malassezia furfur''. Furthermore, langerin recognizes Gal-6-sulfated lactosamine of
glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ...
. In the
respiratory epithelium Respiratory epithelium, or airway epithelium, is a type of ciliated columnar epithelium found lining most of the respiratory tract as respiratory mucosa, where it serves to moisten and protect the airways. It is not present in the vocal cords o ...
, LCs recognize
measles virus ''Measles morbillivirus'' (MeV), also called measles virus (MV), is a single-stranded, negative-sense, enveloped, non-segmented RNA virus of the genus '' Morbillivirus'' within the family '' Paramyxoviridae''. It is the cause of measles. Human ...
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 Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side ...
for
valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotona ...
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 Asparagine (symbol Asn or N) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...
for aspartic acid in the 288. position leads to 10-fold reduction in the ability to recognize mannose-BSA. A substitution of
tryptophane Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...
for arginine in the 264. position leads to a loss of
Birbeck granules Birbeck granules, also known as Birbeck bodies, are rod shaped or "tennis-racket" cytoplasmic organelles with a central linear density and a striated appearance. First described in 1961 (where they were simply termed "characteristic granules"), the ...
.


See also

*
Paul Langerhans Paul Langerhans (25 July 1847 – 20 July 1888) was a German pathologist, physiologist and biologist, credited with the discovery of the cells that secrete insulin, named after him as the islets of Langerhans. Eponymous terms * Islets of Langerh ...
*
Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...


References


Further reading

* * * * * * * * * * * * *


External links

* * {{Clusters of differentiation Transmembrane receptors Proteins Glycobiology C-type lectins