CD1d molecule | CD molecules | IUPHAR Guide to IMMUNOPHARMACOLOGY

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CD1d molecule

  Target has curated data in GtoImmuPdb

Target id: 2997

Nomenclature: CD1d molecule

Family: CD molecules

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 335 1q23.1 CD1D CD1d molecule
Mouse 1 336 3 F1; 3 37.91 cM Cd1d1 CD1d1 antigen
Mouse 1 336 3 F1; 3 37.88 cM Cd1d2 CD1d2 antigen
Rat 1 336 2q34 Cd1d1 CD1d1 molecule
Gene and Protein Information Comments
Two mouse homologs for human CD1d have been identified, Cd1d1 (MGI:107674) and Cd1d2 (MGI:107675). These two mouse isoforms present different sets of self-antigen(s) in the mouse thymus, and thus have an impact on iNKT cell development in the mouse [11]. The 336 aa isoform 1 from mouse Cd1d2 encodes a functional protein in 129, NMRI, AKR/J, and other mouse strains, but not in C57BL/6 mice.
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Parameter Reference
AH10-7 Hs Binding - - 3
[3]
Immunopharmacology Comments
CD1d is a lipid-binding MHC class I-like protein that is expressed by dendritic cells. CD1d presents self and microbial lipid/glycolipid antigens to unconventional T cells known as invariant natural killer T (iNKT) cells [2,13]. The iNKT cells are activated by interaction of the CD1d-glycolipid complex with the T cell receptor and an immune response is initiated.

Synthetic glycolipid-like ligands that bind CD1d have been developed as immunomodulators and there has been some investigation of these as anti-cancer immunotherapy [1,5,7,13] (e.g. KRN7000 [4,6,10], although this agent has shown limited clinical efficacy for various reasons[8,14]). Activation of iNKT cells via CD1d may also be applicable for the treatment of autoimmune diseases [9,12].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0045089 positive regulation of innate immune response TAS
click arrow to show/hide IEA associations
GO:0045087 innate immune response IEA
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 2 GO processes
GO:0048006 antigen processing and presentation, endogenous lipid antigen via MHC class Ib IDA
GO:0048007 antigen processing and presentation, exogenous lipid antigen via MHC class Ib IBA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 2 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
GO:0045058 T cell selection TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
GO:0045089 positive regulation of innate immune response TAS
GO:0050776 regulation of immune response TAS
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0045058 T cell selection TAS
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
GO:0045058 T cell selection TAS

References

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1. Banchet-Cadeddu A, Hénon E, Dauchez M, Renault JH, Monneaux F, Haudrechy A. (2011) The stimulating adventure of KRN 7000. Org. Biomol. Chem., 9 (9): 3080-104. [PMID:21394364]

2. Chen X, Wang X, Keaton JM, Reddington F, Illarionov PA, Besra GS, Gumperz JE. (2007) Distinct endosomal trafficking requirements for presentation of autoantigens and exogenous lipids by human CD1d molecules. J. Immunol., 178 (10): 6181-90. [PMID:17475845]

3. Chennamadhavuni D, Saavedra-Avila NA, Carreño LJ, Guberman-Pfeffer MJ, Arora P, Yongqing T, Koay HF, Godfrey DI, Keshipeddy S, Richardson SK et al.. (2018) Dual Modifications of α-Galactosylceramide Synergize to Promote Activation of Human Invariant Natural Killer T Cells and Stimulate Anti-tumor Immunity. Cell Chem Biol, 25 (5): 571-584.e8. [PMID:29576533]

4. Giaccone G, Punt CJ, Ando Y, Ruijter R, Nishi N, Peters M, von Blomberg BM, Scheper RJ, van der Vliet HJ, van den Eertwegh AJ et al.. (2002) A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors. Clin. Cancer Res., 8 (12): 3702-9. [PMID:12473579]

5. Godfrey DI, Le Nours J, Andrews DM, Uldrich AP, Rossjohn J. (2018) Unconventional T Cell Targets for Cancer Immunotherapy. Immunity, 48 (3): 453-473. [PMID:29562195]

6. Ishikawa A, Motohashi S, Ishikawa E, Fuchida H, Higashino K, Otsuji M, Iizasa T, Nakayama T, Taniguchi M, Fujisawa T. (2005) A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. Clin. Cancer Res., 11 (5): 1910-7. [PMID:15756017]

7. Krijgsman D, Hokland M, Kuppen PJK. (2018) The Role of Natural Killer T Cells in Cancer-A Phenotypical and Functional Approach. Front Immunol, 9: 367. [PMID:29535734]

8. Nair S, Dkodapkar MV. (2017) Natural Killer T Cells in Cancer Immunotherapy. Frontiers in Immunology, 8: 1178.

9. Podbielska M, O'Keeffe J, Hogan EL. (2018) Autoimmunity in multiple sclerosis: role of sphingolipids, invariant NKT cells and other immune elements in control of inflammation and neurodegeneration. J. Neurol. Sci., 385: 198-214. [PMID:29406905]

10. Schneiders FL, Scheper RJ, von Blomberg BM, Woltman AM, Janssen HL, van den Eertwegh AJ, Verheul HM, de Gruijl TD, van der Vliet HJ. (2011) Clinical experience with α-galactosylceramide (KRN7000) in patients with advanced cancer and chronic hepatitis B/C infection. Clin. Immunol., 140 (2): 130-41. [PMID:21169066]

11. Sundararaj S, Zhang J, Krovi SH, Bedel R, Tuttle KD, Veerapen N, Besra GS, Khandokar Y, Praveena T, Le Nours J et al.. (2018) Differing roles of CD1d2 and CD1d1 proteins in type I natural killer T cell development and function. Proc. Natl. Acad. Sci. U.S.A., 115 (6): E1204-E1213. [PMID:29351991]

12. Van Kaer L, Wu L. (2018) Therapeutic Potential of Invariant Natural Killer T Cells in Autoimmunity. Front Immunol, 9: 519. [PMID:29593743]

13. Wolf BJ, Choi JE, Exley MA. (2018) Novel Approaches to Exploiting Invariant NKT Cells in Cancer Immunotherapy. Front Immunol, 9: 384. [PMID:29559971]

14. Yu KO, Porcelli SA. (2005) The diverse functions of CD1d-restricted NKT cells and their potential for immunotherapy. Immunol. Lett., 100 (1): 42-55. [PMID:16083968]

How to cite this page

CD molecules: CD1d molecule. Last modified on 29/08/2018. Accessed on 26/04/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2997.