CD282 TLR2 (Toll-like receptor 2), TIL4
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Monocyte
Neutrophil
Granulocyte
Macrophage
Dendritic Cell
Keratinocyte
Liver
Lung
Spleen
Bone Marrow
Lymph Node
Peripheral blood
Leukocyte
85 / 85

Expression
CD282 is expressed on macrophages, granulocytes, keratinocytes, peripheral blood leukocytes, dendritic cells and neutrophils.  Expression is high in monocytes in bone marrow, lymph node, spleen, lung, fetal liver and in breast milk but levels are low in other tissues.

Structure
MOLECULAR FAMILY NAME: Belongs to the Toll-like receptor family.

CD282 is a single-pass type-1 766  aa glycoprotein.  It contains an 18 aa signal sequence, a 570 aa extracellular domain which contains 14 leucine-rich repeats (LLR) capped at each end by N- and C-terminal motifs which are capped at each end by N- and C-terminal motifs and has 4 potential N-linked glycosylation sites, a 21 aa transmembrane domain and an 175 aa cytoplasmic domain containing a Toll/IL-1R domain that interacts with the adaptor protein TIR domain-containing adaptor protein (TIRAP).  The LRRs are predicted to have a "horse-like" structure and form the ligand binding domain.  CD282 forms heterodimers with CD281 and CD286. 

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

Glycosylation of Ans-442 is critical for secretion of the N-terminal ecodomain of CD282.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD282

CD282 associates with CD281 (TLR1) or CD286 (TLR6), lipoproteins and glycans.

Function
CD282 plays a fundamental role in pathogen recognition and activation of innate immunity.  TLRs are highly conserved from Drosophilia to humans and share structural and functional similarities.  CD282 functions as a pattern recognition receptor for pathogen-associated molecular patterns (PAMPs) of fungi, protozoan pathogens and bacteria, particulary peptidoglycan and lipoteochoic acids of Gram-negative bacteria.  PAMPs are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity.  Ligand binding CD282 recruits TIRAP and leads to myeloid differentiation primary response gene 88 (MyD88) dependent signaling resulting in NF-κB activation and pro-inflammatory cytokine production and it initiates an acquired immune reponse.  CD282 cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. CD282 is reported to bind to a diverse range of bacterial cell wall components, mediating the innate immune response in co-operation with MD-2.  It acts via MyD88 and TRAF6, leading to NF-κB activation, cytokine secretion and the inflammatory response.  LY96 and CD286 (TLR6) binds via the extracellular domain and MyD88 binds via their respective TIR domains.  The wide range of bacterial components recognized by CD282 is in part due to its association with CD281 and CD286 which enables discrimination of subtle structural differences between lipopeptides.  CD282 may promote apoptosis in response to lipoproteins.  Studies of the role of CD282 on T cells suggest CD282 acts as a costimulatory receptor for antigen-specific T cell development and is involved in maintenance of T cell memory.  CD282 deficient mice are significantly more susceptible to infection with Gram-positive bacteria than wild mice.
 
BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD282 IN INTACT ANIMAL

Lipoproteins from Borrelia burgdorferi expressing CD282 suggests that the CD282 recognition is revelant to natural Borrelia infection.  In addition, CD92 responses using whole Mycobacterium avium and Staphylococcus aureus, demonstrated that this receptor can function as a signal transducer for a wide spectrum of bacterial products.  It has been concluded that diverse pathogens activate cells though CD282 and propose that this molecule is a central pattern recognition receptor in host immune responses to microbial invasion.  Single nucleotide polymorphisms (SNPs) of CD282 have been associated with increased susceptibility to some human infectious diseases, including lepromatous leprosy, tuberculosis amd atopic diseases such as dermatitis and asthma.  There is recognition of mycoplasmal macrophages-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin and B.burgdorferi outer surface protein.  A lipoprotein (OspA-L) cooperatively with TLR6.


Comments
MOLECULAR INERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD282: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD282: No information.

ADDITIONAL INSIGHTS

For further information see Lien, E. et al (1999) J. Biol. Chem. 274: 33419-33425.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 7097O60603
Antibodies

Revised June 25, 2008


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