User:KarolinaKnížková/sandbox
CD1b[edit]
| Gene lokus | 1q23.1 |
|---|---|
| Molecular mass (Da) | 36939 |
| Ag-binding cleft size (Å) | 2,3 |
| Lenght of antigens (carbons) | 25-80 |
CD1b belongs to group 1 of CD1 family of transmembrane glycoproteins. CD1 molecules are expressed on the surface of numerous different human antigen presenting cells (DCs, monocytes and some thymocytes). This specialised group of glycoproteins present self and non-self lipid-based antigens to specific αβ T-cells.[1] CD1 molecules are structurally related to major histocopatibility complex (MHC), they belongs to MHC class I-like genes. The human CD1 locus is lokalizate on chromosome 1 and contains five nonpolymorphic genes (CD1a, CD1b, CD1c, CD1d and CD1e).[2][3]
Structure and function[edit]
CD1b molecules (as well as other CD1 and classical MHC I molecules) are formed by membrane-bound glycoprotein composed of three extracellular domains (α1,α2,α3). These extracellular domains are non-covalently associated with β2 microglobulin (which has the function of stabilising protein). This organization forms a narrow hydrophobic binding groove that accommodates lipid-based antigens. Binding groove is made up of four broadly interconnected pockets that are occupied by the alkyl chains of glycolipid and two detergent molecules.[4][5] Compared to others CD1 molecules this unique arrangement of CD1b provides a possibility to bind a wide spectrum of antigens with various lenght of alkyl chains. Alkyl components of antigens are attached in hydrophobic groove and a hydrophilic part stands out from CD1b molecule and thus provides to the TCR a place to bind.[6]
CD1b molecule has the largest antigen binding cleft within the CD1 family. Whereas the microbial lipids tend to have longer alkyl chains than self endogeneous lipids it seems that CD1b is specifically adapted to present microbial lipids (rather than endogeneous) to T cells.[5]
Diseases[edit]
In case when immune system doesn't distinguish self and non-self structures it leads to autoreactive T-cell response. Autoreactive CD1b can recognize for example phospatidylglycerol, which is common for mammalian mitochodria and also bacteria. This autoantigen is released during a bacterial infection or mitochondrial stress. CD1b also presents endogenous gangliosides to specific T cells so they can commence autoimmune diseases such as multiple sclerosis.
Because CD1 molecules in contrast with major histocompatibility complex have restricted diversity, it could be an interesting marker for imunotherapy and target for development of new drugs.[7]
Reference[edit]
- ^ Rossjohn, Jamie; Moody, D. Branch; Nours, Jérôme Le; Gapin, Laurent; Tuttle, Kathryn D.; Hanim Halim; Tan, Li Lynn; Bhati, Mugdha; Cheng, Tan-Yun (2016-10-27). "T cell receptor recognition of CD1b presenting a mycobacterial glycolipid". Nature Communications. 7: 13257. doi:10.1038/ncomms13257. ISSN 2041-1723.
- ^ "CD1B CD1b molecule [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-02-06.
- ^ Porcelli, Steven A.; Peters, Peter J.; Modlin, Robert L.; Sugita, Masahiko; Niazi, Kayvan R.; Rogers, Rick A.; Moody, D. Branch; Lee, Agnes; Stenger, Steffen (1998-03-01). "The Tyrosine-Containing Cytoplasmic Tail of CD1b Is Essential for Its Efficient Presentation of Bacterial Lipid Antigens". Immunity. 8 (3): 341–351. doi:10.1016/S1074-7613(00)80539-7. ISSN 1074-7613. PMID 9529151.
- ^ "CD1B - T-cell surface glycoprotein CD1b precursor - Homo sapiens (Human) - CD1B gene & protein". www.uniprot.org. Retrieved 2019-02-06.
- ^ a b Cerundolo, Vincenzo; Jones, E. Yvonne; Schmidt, Richard R.; Ritter, Gerd; Castro-Palomino, Julio C.; Shepherd, Dawn; Harlos, Karl; Zaccai, Nathan R.; Gadola, Stephan D. (2002-08). "Structure of human CD1b with bound ligands at 2.3 Å, a maze for alkyl chains". Nature Immunology. 3 (8): 721–726. doi:10.1038/ni821. ISSN 1529-2916.
{{cite journal}}: Check date values in:|date=(help) - ^ Jones, E. Yvonne; Cerundolo, Vincenzo; Besra, Gurdyal S.; Fersht, Alan R.; Zaccai, Nathan R.; Gibson, Kevin J. C.; Gadola, Stephan D.; Shepherd, Dawn; Batuwangala, Thil (2004-02-15). "The Crystal Structure of Human CD1b with a Bound Bacterial Glycolipid". The Journal of Immunology. 172 (4): 2382–2388. doi:10.4049/jimmunol.172.4.2382. ISSN 0022-1767. PMID 14764708.
- ^ Van Rhijn, Ildiko; van Berlo, Twan; Hilmenyuk, Tamara; Cheng, Tan-Yun; Wolf, Benjamin J.; Tatituri, Raju V. V.; Uldrich, Adam P.; Napolitani, Giorgio; Cerundolo, Vincenzo (2016-01-12). "Human autoreactive T cells recognize CD1b and phospholipids". Proceedings of the National Academy of Sciences of the United States of America. 113 (2): 380–385. doi:10.1073/pnas.1520947112. ISSN 0027-8424. PMC 4720340. PMID 26621732.
{{cite journal}}: CS1 maint: PMC format (link)
Literature[edit]
MURPHY, Kenneth a Casey WEAVER. Janeway's immunobiology. 9th edition. New York, NY: Garland Science/Taylor & Francis Group, [2016]. ISBN 978-0-8153-4551-0