KIR3DL2 (CD158K) | CD molecules | IUPHAR/BPS Guide to PHARMACOLOGY

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KIR3DL2 (CD158K)

target has curated data in GtoImmuPdb

Target id: 3067

Nomenclature: KIR3DL2 (CD158K)

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 1 455 19q13.42 KIR3DL2 killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 2
Mouse 1 409 Chromosome X, 58.77 cM Kir3dl1 killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 1
Gene and Protein Information Comments
Alternatively spliced transcript variants that encode different protein isoforms have been identified for human KIR3DL2 [2] and its mouse ortholog Kir3dl1.
Previous and Unofficial Names
killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 1 | killer cell immunoglobulin-like receptor | cl-5 | Kirl1 (Mm) | nkat4 | nkat4a
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Antibody Comments
Innate Pharma are developing the anti-KIR3DL2 monoclonal antibody IPH4102 for cutaneous T-cell lymphomas (CTCL) [1,5,9]. IPH4102 has been granted orphan drug status in the European Union and in the United States for the treatment of CTCL, and in January 2019 received FDA fast track designation for Sézary syndrome, to expedite its development and regulatory review in this patient subset (based on preliminary Phase I results that demonstrated significant clinical activity [6]).
Immunopharmacology Comments
KIR3DL2 mediates NK cell coinhibitory signals when it binds to MHC class I molecules on other cells. Binding to HLA-A3 , HLA-A11 [3] and HLA-B27 [4] has been reported, as has binding to CpG oligodeoxynucleotides [7].

KIR3DL2 is highly expressed on the malignant cells in cutaneous T-cell lymphoma (CTCL), including mycosis fungoides and Sézary syndrome, and has been reported to promote resistance to NK cell-induced cell death in some CTCLs [8]. Blockade of the suppressive signal mediated by KIR3DL2 using a monoclonal antibody (Innate Pharma's IPH4102) is being investigated as a therapeutic approach for the treatment of T cell lymphomas such as Sézary syndrome [5-6,9].
Immuno Process Associations
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0050776 regulation of immune response TAS
General Comments
KIR3DL2 is one of a family of 18 human genes that encode MHC class I receptors on the surface of nautral killer (NK) cells and some cytotoxic T cell subsets (HGNC gene group link: Killer cell immunoglobulin like receptors (KIR)). Most KIR proteins mediate inhibitory signals that suppress the cytotoxic activity of the NK cell on which they are expressed. KIR3DL2 is an immuno-oncology therapeutic target.

References

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1. Bonnafous C, Sicard H, Buffet R. (2014) A compound that specifically binds to kir3dl2 for use in the treatment of peripheral t cell lymphoma. Patent number: WO2014128221A1. Assignee: Innate Pharma. Priority date: 20/02/2013. Publication date: 28/08/2014.

2. Döhring C, Samaridis J, Colonna M. (1996) Alternatively spliced forms of human killer inhibitory receptors. Immunogenetics, 44 (3): 227-30. [PMID:8662091]

3. Hansasuta P, Dong T, Thananchai H, Weekes M, Willberg C, Aldemir H, Rowland-Jones S, Braud VM. (2004) Recognition of HLA-A3 and HLA-A11 by KIR3DL2 is peptide-specific. Eur. J. Immunol., 34 (6): 1673-9. [PMID:15162437]

4. Kollnberger S, Chan A, Sun MY, Chen LY, Wright C, di Gleria K, McMichael A, Bowness P. (2007) Interaction of HLA-B27 homodimers with KIR3DL1 and KIR3DL2, unlike HLA-B27 heterotrimers, is independent of the sequence of bound peptide. Eur. J. Immunol., 37 (5): 1313-22. [PMID:17407096]

5. Marie-Cardine A, Viaud N, Thonnart N, Joly R, Chanteux S, Gauthier L, Bonnafous C, Rossi B, Bléry M, Paturel C et al.. (2014) IPH4102, a humanized KIR3DL2 antibody with potent activity against cutaneous T-cell lymphoma. Cancer Res., 74 (21): 6060-70. [PMID:25361998]

6. Sicard H, Bonnafous C, Morel A, Bagot M, Bensussan A, Marie-Cardine A. (2015) A novel targeted immunotherapy for CTCL is on its way: Anti-KIR3DL2 mAb IPH4102 is potent and safe in non-clinical studies. Oncoimmunology, 4 (9): e1022306. [PMID:26405593]

7. Sivori S, Falco M, Carlomagno S, Romeo E, Soldani C, Bensussan A, Viola A, Moretta L, Moretto A. (2010) A novel KIR-associated function: evidence that CpG DNA uptake and shuttling to early endosomes is mediated by KIR3DL2. Blood, 116: 1637-1647. DOI: 10.1182/blood-2009-12-256586

8. Thonnart N, Caudron A, Legaz I, Bagot M, Bensussan A, Marie-Cardine A. (2014) KIR3DL2 is a coinhibitory receptor on Sézary syndrome malignant T cells that promotes resistance to activation-induced cell death. Blood, 124: 3330-3332. DOI: 10.1182/blood-2014-09-598995

9. Van Der Weyden C, Bagot M, Neeson P, Darcy PK, Prince HM. (2018) IPH4102, a monoclonal antibody directed against the immune receptor molecule KIR3DL2, for the treatment of cutaneous T-cell lymphoma. Expert Opin Investig Drugs, 27 (8): 691-697. [PMID:30001170]

How to cite this page

CD molecules: KIR3DL2 (CD158K). Last modified on 06/08/2019. Accessed on 23/01/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3067.