CD1D
CD1D is the human gene that encodes the protein CD1d,[5] a member of the CD1 (cluster of differentiation 1) family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are non-classical MHC proteins, related to the class I MHC proteins, and are involved in the presentation of lipid antigens to T cells. CD1d is the only member of the group 2 CD1 molecules.
Biological significance
CD1d-presented lipid antigens activate a special class of T cells, known as natural killer T (NKT) cells, through the interaction with the T-cell receptor present on NKT membranes.[5] When activated, NKT cells rapidly produce Th1 and Th2 cytokines, typically represented by interferon-gamma and interleukin 4 production.
Nomenclature
CD1d is also known as R3G1
Ligands
Some of the known ligands for CD1d are:
- α-galactosylceramide (α-GalCer), a compound originally derived from the marine sponge Agelas mauritanius[6] with no physiological role but great research utility.
- α-glucuronyl- and α-galacturonyl- ceramides, a family of compounds of microbial origin which can be found, for example, on the cell wall of Sphingomonas, a ubiquitous Gram-negative bacterium.[7] The related β-D-glucopyranosylceramide is accumulated in antigen-presenting cells after infection, where it serves to activate invariant NKTs (iNKTs), a special kind of NKT.
- iGb3, a self antigen which has been implied in iNKT selection.[8]
- HS44, a synthetic amino cyclitolic ceramide analogue which has less contact with the TCR, activating iNKTs in a more constrained way than α-GalCer (specially in relation to Th2 cytokines production) and thus being more interesting for therapeutic use.[9]
CD1d tetramers
CD1d tetramers are protein constructs composed of four CD1d molecules joined together and usually fluorescently labelled, used to identify NKT cells or other CD1d-reactive cells. In particular, type I NKT cells and some type II NKT cells are stained by them. A differentiation of these two types can be obtained in human by using an antibody against the TCR Vα24 chain, which is specific of type I NKT cells.[10]
Although they are the most widely used of CD1d oligomers, sometimes CD1d dimers (two units) or pentamers (five units) are used instead.[10]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000158473 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028076 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "P15813 (CD1D_HUMAN)". Uniprot. Retrieved 1 March 2013.
- ^ Franck, Richard W. (1 January 2012). "C-Galactosylceramide: Synthesis and Immunology". C R Chim. 15 (1): 46–56. doi:10.1016/j.crci.2011.05.006. PMC 3293403. PMID 22408579.
- ^ Bendelac, A; Savage PB; Teyton I (2007). "The Biology of NKT Cells". Annual Review of Immunology. 25 (1): 297–336. doi:10.1146/annurev.immunol.25.022106.141711. PMID 17150027.
- ^ Zhou, D (August 2006). "The immunological function of iGb3". Current Protein & Peptide Science. 7 (4): 325–323. doi:10.2174/138920306778018007. PMID 16918447.
- ^ J. Kerzerho; E. Yu; C. M. Barra; E. Alari-Pahissa; E. Girardi; Y. Harrak; P. Lauzurica; A. Llebaria; D. Zajonc; O. Akbari; A. R. Castaño (2012). "Structural and functional characterization of a novel non-glycosidic iNKT agonist with immunomodulatory properties". Journal of Immunology. 188: 2254–2265. doi:10.4049/jimmunol.1103049. PMID 22301545.
- ^ a b Terabe, Masaki; Berzofsky, Jay A. (2008). "The Role of NKT Cells in Tumor Immunity". Adv Cancer Res. 101: 277–348. doi:10.1016/S0065-230X(08)00408-9. PMC 2693255. PMID 19055947.
Further reading
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External links
- CD1d+antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)