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.

CD1D
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4WO4, 1ZT4, 2PO6, 3HUJ, 3SDX, 3TZV, 3U0P, 3VWJ, 3VWK, 4EN3, 4LHU, 4MNG, 4MQ7, 4WW2
Identifiers
Aliases	CD1D, CD1A, R3, R3G1, CD1d molecule
External IDs	OMIM: 188410 MGI: 107674 HomoloGene: 1337 GeneCards: CD1D
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q23.1 Start 158,178,030 bp[1] End 158,186,427 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 F1|3 37.91 cM Start 86,995,834 bp[2] End 86,999,441 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • beta-2-microglobulin binding • lipopeptide binding • histone binding • endogenous lipid antigen binding • lipid antigen binding • exogenous lipid antigen binding • cell adhesion molecule binding • GO:0001948 protein binding Cellular component • cytoplasm • integral component of membrane • endosome • endoplasmic reticulum membrane • membrane • integral component of plasma membrane • cell surface • lysosomal membrane • basolateral plasma membrane • lysosome • endosome membrane • cell membrane • endoplasmic reticulum • extracellular • external side of plasma membrane Biological process • immune system process • T cell selection • heterotypic cell-cell adhesion • positive regulation of T cell proliferation • detection of bacterium • positive regulation of innate immune response • antigen processing and presentation, exogenous lipid antigen via MHC class Ib • innate immune system • GO:0022415 viral process • antigen processing and presentation, endogenous lipid antigen via MHC class Ib • regulation of immune response • positive regulation of T cell mediated cytotoxicity • immune response Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	912	12479
Ensembl	ENSG00000158473	ENSMUSG00000028076
UniProt	P15813	P11609
RefSeq (mRNA)	NM_001766 NM_001319145 NM_001371761 NM_001371762 NM_001371763	NM_007639 NM_001379501 NM_001379502 NM_001379503
RefSeq (protein)	NP_001306074 NP_001757 NP_001358690 NP_001358691 NP_001358692	NP_031665 NP_001366430 NP_001366431 NP_001366432
Location (UCSC)	Chr 1: 158.18 – 158.19 Mb	Chr 3: 87 – 87 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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

1. GRCh38: Ensembl release 89: ENSG00000158473 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028076 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "P15813 (CD1D_HUMAN)". Uniprot. Retrieved 1 March 2013.
6. Franck, Richard W. (1 January 2012). "C-Galactosylceramide: Synthesis and Immunology". Comptes Rendus Chimie. 15 (1): 46–56. doi:10.1016/j.crci.2011.05.006. PMC 3293403. PMID 22408579.
7. 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.
8. Zhou, D (August 2006). "The immunological function of iGb3". Current Protein & Peptide Science. 7 (4): 325–333. doi:10.2174/138920306778018007. PMID 16918447.
9. 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 (5): 2254–2265. doi:10.4049/jimmunol.1103049. PMC 3288653. PMID 22301545.
10. 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

• Melián A, Beckman EM, Porcelli SA, Brenner MB (1996). "Antigen presentation by CD1 and MHC-encoded class I-like molecules". Curr. Opin. Immunol. 8 (1): 82–88. doi:10.1016/S0952-7915(96)80109-9. PMID 8729450.
• Joyce S (2001). "CD1d and natural T cells: how their properties jump-start the immune system". Cell. Mol. Life Sci. 58 (3): 442–469. doi:10.1007/PL00000869. PMID 11315191.
• Sköld M, Behar SM (2003). "Role of CD1d-Restricted NKT Cells in Microbial Immunity". Infect. Immun. 71 (10): 5447–5455. doi:10.1128/IAI.71.10.5447-5455.2003. PMC 201095. PMID 14500461.
• Brigl M, Brenner MB (2004). "CD1: antigen presentation and T cell function". Annu. Rev. Immunol. 22 (1): 817–890. doi:10.1146/annurev.immunol.22.012703.104608. PMID 15032598.
• Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects". Curr. HIV Res. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID 16454711.
• Brutkiewicz RR (2006). "CD1d ligands: the good, the bad, and the ugly". J. Immunol. 177 (2): 769–775. doi:10.4049/jimmunol.177.2.769. PMID 16818729.
• Blumberg RS, Terhorst C, Bleicher P, et al. (1991). "Expression of a nonpolymorphic MHC class I-like molecule, CD1D, by human intestinal epithelial cells". J. Immunol. 147 (8): 2518–2524. PMID 1717564.
• Balk SP, Bleicher PA, Terhorst C (1989). "Isolation and characterization of a cDNA and gene coding for a fourth CD1 molecule". Proc. Natl. Acad. Sci. U.S.A. 86 (1): 252–256. Bibcode:1989PNAS...86..252B. doi:10.1073/pnas.86.1.252. PMC 286442. PMID 2463622.
• Calabi F, Jarvis JM, Martin L, Milstein C (1989). "Two classes of CD1 genes". Eur. J. Immunol. 19 (2): 285–292. doi:10.1002/eji.1830190211. PMID 2467814.
• Yu CY, Milstein C (1990). "A physical map linking the five CD1 human thymocyte differentiation antigen genes". EMBO J. 8 (12): 3727–3732. doi:10.1002/j.1460-2075.1989.tb08548.x. PMC 402056. PMID 2583117.
• Martin LH, Calabi F, Milstein C (1987). "Isolation of CD1 genes: a family of major histocompatibility complex-related differentiation antigens". Proc. Natl. Acad. Sci. U.S.A. 83 (23): 9154–9158. doi:10.1073/pnas.83.23.9154. PMC 387093. PMID 3097645.
• Balk SP, Burke S, Polischuk JE, et al. (1994). "Beta 2-microglobulin-independent MHC class Ib molecule expressed by human intestinal epithelium". Science. 265 (5169): 259–262. doi:10.1126/science.7517575. PMID 7517575.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Kawano T, Cui J, Koezuka Y, et al. (1997). "CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides". Science. 278 (5343): 1626–1629. Bibcode:1997Sci...278.1626K. doi:10.1126/science.278.5343.1626. PMID 9374463.
• Katabami S, Matsuura A, Chen HZ, et al. (1998). "Structural organization of rat CD1 typifies evolutionarily conserved CD1D class genes". Immunogenetics. 48 (1): 22–31. doi:10.1007/s002510050396. PMID 9601940.
• Somnay-Wadgaonkar K, Nusrat A, Kim HS, et al. (1999). "Immunolocalization of CD1d in human intestinal epithelial cells and identification of a beta2-microglobulin-associated form". Int. Immunol. 11 (3): 383–392. doi:10.1093/intimm/11.3.383. PMID 10221650.
• Campbell NA, Kim HS, Blumberg RS, Mayer L (1999). "The nonclassical class I molecule CD1d associates with the novel CD8 ligand gp180 on intestinal epithelial cells". J. Biol. Chem. 274 (37): 26259–26265. doi:10.1074/jbc.274.37.26259. PMID 10473580.
• Han M, Hannick LI, DiBrino M, Robinson MA (2000). "Polymorphism of human CD1 genes". Tissue Antigens. 54 (2): 122–127. doi:10.1034/j.1399-0039.1999.540202.x. PMID 10488738.

External links

• CD1d+antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human CD1A genome location and CD1A gene details page in the UCSC Genome Browser.
• Human CD1D genome location and CD1D gene details page in the UCSC Genome Browser.