leukocyte immunoglobulin like receptor B1 (CD85j)

Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2973

Nomenclature: leukocyte immunoglobulin like receptor B1 (CD85j)

Abbreviated Name: LILRB1

Family: CD molecules, Other immune checkpoint proteins

Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	1	650	19q13.42	LILRB1	leukocyte immunoglobulin like receptor B1
Gene and Protein Information Comments
Multiple transcript variants encoding different isoforms have been found for the human gene. We provide the RefSeqs and gene/protein information for isoform 1.

Previous and Unofficial Names
ILT2 \| leucocyte Ig-like receptor B1 \| leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 1 \| LIR-1 \| LIR1 \| MIR-7 \| myeloid inhibitory receptor 7 \| PIR-B \| PIRB

Previous and Unofficial Names

ILT2 | leucocyte Ig-like receptor B1 | leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 1 | LIR-1 | LIR1 | MIR-7 | myeloid inhibitory receptor 7 | PIR-B | PIRB

Database Links
Alphafold	Q8NHL6 (Hs)
Ensembl Gene	ENSG00000104972 (Hs)
Entrez Gene	10859 (Hs)
Human Protein Atlas	ENSG00000104972 (Hs)
KEGG Gene	hsa:10859 (Hs)
OMIM	604811 (Hs)
Pharos	Q8NHL6 (Hs)
RefSeq Nucleotide	NM_006669 (Hs)
RefSeq Protein	NP_006660 (Hs)
UniProtKB	Q8NHL6 (Hs)
Wikipedia	LILRB1 (Hs)

Immunopharmacology Comments
LILRB1 (CD85j) is a member of the inhibitory leukocyte immunoglobulin like receptor (LILRB) family (HGNC family 1182). It acts as an inhibitory immune checkpoint for B cell function. Ligands identified for LILRB include native MHC class I proteins, some HLA molecules, pathogen-derived ligands (e.g. from CMV, Dengue virus and some bacteria) and host immunomodulatory proteins such as S100 calcium binding protein A9 (S100A9; P06702; which also binds TLR4 and RAGE) [2]. Expression of LILRB1 by macrophages (including tumour-associated macrophages) facilitates binding to MHC class I, and this interaction mediates an inhibitory signal that negatively regulates phagocytosis [1]. In addition, cancer cells that express LILRB1 are protected from macrophage phagocytosis, and when either LILRB1 or MHC class I expression by cancer cells is disrupted in vitro and in vivo, phagocytosis resumes. These findings suggest LILRB1 as a novel immuno-oncology target. LILRB1 has been identified as a potential molecular receptor for Plasmodium falciparum-coded proteins that are expressed by infected host erythrocytes. Interaction of these parasite RIFIN proteins (encoded by rif genes [3]) and inhibitory leukocyte receptors such as LILRB1 appears to mediate parasite-driven evasion of the host's immune system by inhibiting activation of LILRB1-expressing B cells and natural killer (NK) cells [6].

Immunopharmacology Comments

LILRB1 (CD85j) is a member of the inhibitory leukocyte immunoglobulin like receptor (LILRB) family (HGNC family 1182). It acts as an inhibitory immune checkpoint for B cell function. Ligands identified for LILRB include native MHC class I proteins, some HLA molecules, pathogen-derived ligands (e.g. from CMV, Dengue virus and some bacteria) and host immunomodulatory proteins such as S100 calcium binding protein A9 (S100A9; P06702; which also binds TLR4 and RAGE) [2].

Expression of LILRB1 by macrophages (including tumour-associated macrophages) facilitates binding to MHC class I, and this interaction mediates an inhibitory signal that negatively regulates phagocytosis [1]. In addition, cancer cells that express LILRB1 are protected from macrophage phagocytosis, and when either LILRB1 or MHC class I expression by cancer cells is disrupted in vitro and in vivo, phagocytosis resumes. These findings suggest LILRB1 as a novel immuno-oncology target.

LILRB1 has been identified as a potential molecular receptor for Plasmodium falciparum-coded proteins that are expressed by infected host erythrocytes. Interaction of these parasite RIFIN proteins (encoded by rif genes [3]) and inhibitory leukocyte receptors such as LILRB1 appears to mediate parasite-driven evasion of the host's immune system by inhibiting activation of LILRB1-expressing B cells and natural killer (NK) cells [6].

Cell Type Associations

Immuno Cell Type:	B cells
Cell Ontology Term:	plasma cell (CL:0000786)
Comment:	Loss of LILRB1 on malignant plasma cells plays a role in immune escape in multiple myeloma. In contrast, overexpression of LILRB1 increases susceptibility to T cell- and NK-mediated killing.
References:	5

Immuno Cell Type:	Macrophages & monocytes
Cell Ontology Term:	macrophage (CL:0000235)
Comment:	Expression of LILRB1 by macrophages mediates an inhibitory signal that negatively regulates phagocytosis [1]. The protective effect of LILRB1 expression is exploited by some cancers, to avoid immune system-mediated destruction.

Immuno Process Associations

Immuno Process:

Inflammation

GO Annotations:

Associated to 4 GO processes

GO:0002309	T cell proliferation involved in immune response	IDA
GO:0045953	negative regulation of natural killer cell mediated cytotoxicity	IDA
GO:2001189	negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell	IDA
GO:2001193	positive regulation of gamma-delta T cell activation involved in immune response	IDA

Immuno Process:

Antigen presentation

GO Annotations:

Associated to 2 GO processes

GO:0031623	receptor internalization	TAS
GO:0045806	negative regulation of endocytosis	IDA

Immuno Process:

T cell (activation)

GO Annotations:

Associated to 8 GO processes

GO:0001915	negative regulation of T cell mediated cytotoxicity	IDA
GO:0002309	T cell proliferation involved in immune response	IDA
GO:0042130	negative regulation of T cell proliferation	IDA
GO:0046636	negative regulation of alpha-beta T cell activation	IDA
GO:2001186	negative regulation of CD8-positive, alpha-beta T cell activation	IDA
GO:2001189	negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell	IDA
GO:2001193	positive regulation of gamma-delta T cell activation involved in immune response	IDA
	click arrow to show/hide IEA associations
GO:0002250	adaptive immune response	IEA

Immuno Process:

B cell (activation)

GO Annotations:

Associated to 2 GO processes

GO:0001915	negative regulation of T cell mediated cytotoxicity	IDA
	click arrow to show/hide IEA associations
GO:0002250	adaptive immune response	IEA

Immuno Process:

Immune regulation

GO Annotations:

Associated to 13 GO processes

GO:0001915	negative regulation of T cell mediated cytotoxicity	IDA
GO:0002719	negative regulation of cytokine production involved in immune response	IDA
GO:0002767	immune response-inhibiting cell surface receptor signaling pathway	NAS
GO:0002774	Fc receptor mediated inhibitory signaling pathway	IDA
GO:0042130	negative regulation of T cell proliferation	IDA
GO:0045953	negative regulation of natural killer cell mediated cytotoxicity	IDA
GO:0046636	negative regulation of alpha-beta T cell activation	IDA
GO:0060907	positive regulation of macrophage cytokine production	IDA
GO:2001186	negative regulation of CD8-positive, alpha-beta T cell activation	IDA
GO:2001189	negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell	IDA
GO:2001193	positive regulation of gamma-delta T cell activation involved in immune response	IDA
GO:2001199	negative regulation of dendritic cell differentiation	IMP
GO:2001205	negative regulation of osteoclast development	IDA

Immuno Process:

Immune system development

GO Annotations:

Associated to 2 GO processes

GO:2001199	negative regulation of dendritic cell differentiation	IMP
GO:2001205	negative regulation of osteoclast development	IDA

Immuno Process:

Cytokine production & signalling

GO Annotations:

Associated to 10 GO processes

GO:0002719	negative regulation of cytokine production involved in immune response	IDA
GO:0019221	cytokine-mediated signaling pathway	IBA
GO:0032688	negative regulation of interferon-beta production	IDA
GO:0032689	negative regulation of type II interferon production	IDA
GO:0032693	negative regulation of interleukin-10 production	IDA
GO:0032695	negative regulation of interleukin-12 production	IDA
GO:0032720	negative regulation of tumor necrosis factor production	IDA
GO:0032729	positive regulation of type II interferon production	IDA
GO:0060907	positive regulation of macrophage cytokine production	IDA
GO:0071635	negative regulation of transforming growth factor beta production	IDA

Immuno Process:

Chemotaxis & migration

GO Annotations:

Associated to 5 GO processes

GO:0042130	negative regulation of T cell proliferation	IDA
GO:0046636	negative regulation of alpha-beta T cell activation	IDA
GO:2001186	negative regulation of CD8-positive, alpha-beta T cell activation	IDA
GO:2001189	negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell	IDA
GO:2001193	positive regulation of gamma-delta T cell activation involved in immune response	IDA

Immuno Process:

Cellular signalling

GO Annotations:

Associated to 8 GO processes

GO:0002309	T cell proliferation involved in immune response	IDA
GO:0002767	immune response-inhibiting cell surface receptor signaling pathway	NAS
GO:0002774	Fc receptor mediated inhibitory signaling pathway	IDA
GO:0042130	negative regulation of T cell proliferation	IDA
GO:0046636	negative regulation of alpha-beta T cell activation	IDA
GO:2001186	negative regulation of CD8-positive, alpha-beta T cell activation	IDA
GO:2001189	negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell	IDA
GO:2001193	positive regulation of gamma-delta T cell activation involved in immune response	IDA

Clinically-Relevant Mutations and Pathophysiology

Disease:

Multiple myeloma

Description:	A myeloma that is located in the plasma cells in bone marrow.
Synonyms:	plasma cell myeloma
Disease Ontology:	DOID:9538
OMIM:	254500

Role:

Loss of LILRB1 on malignant plasma cells contributes to immune escape in multiple myeloma.

References:

5

General Comments
LILRB1 binds to MHC class I molecules on human lymphoid and myelomonocytic cells, including natural killer (NK) cells,T cells, B cells, monocytes, macrophages, and dendritic cells [4]. This interaction mediates an inhibitory 'don't-eat-me' signal via cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) contained in the protein's intracellular domain, and this inhibits propagation of an immune response upon recognition of self-MHC class I molecules.

General Comments

LILRB1 binds to MHC class I molecules on human lymphoid and myelomonocytic cells, including natural killer (NK) cells,T cells, B cells, monocytes, macrophages, and dendritic cells [4]. This interaction mediates an inhibitory 'don't-eat-me' signal via cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) contained in the protein's intracellular domain, and this inhibits propagation of an immune response upon recognition of self-MHC class I molecules.

References

Show »« Hide

1. Barkal AA, Weiskopf K, Kao KS, Gordon SR, Rosental B, Yiu YY, George BM, Markovic M, Ring NG, Tsai JM et al.. (2018) Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy. Nat Immunol, 19 (1): 76-84. [PMID:29180808]

2. Burshtyn DN, Morcos C. (2016) The Expanding Spectrum of Ligands for Leukocyte Ig-like Receptors. J Immunol, 196 (3): 947-55. [PMID:26802060]

3. Cheng Q, Cloonan N, Fischer K, Thompson J, Waine G, Lanzer M, Saul A. (1998) stevor and rif are Plasmodium falciparum multicopy gene families which potentially encode variant antigens. Mol Biochem Parasitol, 97 (1-2): 161-76. [PMID:9879895]

4. Colonna M, Navarro F, Bellón T, Llano M, García P, Samaridis J, Angman L, Cella M, López-Botet M. (1997) A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells. J Exp Med, 186 (11): 1809-18. [PMID:9382880]

5. Lozano E, Díaz T, Mena MP, Suñe G, Calvo X, Calderón M, Pérez-Amill L, Rodríguez V, Pérez-Galán P, Roué G et al.. (2018) Loss of the Immune Checkpoint CD85j/LILRB1 on Malignant Plasma Cells Contributes to Immune Escape in Multiple Myeloma. J Immunol, 200 (8): 2581-2591. [PMID:29531171]

6. Saito F, Hirayasu K, Satoh T, Wang CW, Lusingu J, Arimori T, Shida K, Palacpac NMQ, Itagaki S, Iwanaga S et al.. (2017) Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors. Nature, 552 (7683): 101-105. [PMID:29186116]

How to cite this page

CD molecules: leukocyte immunoglobulin like receptor B1 (CD85j). Last modified on 15/05/2018. Accessed on 02/10/2023. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2973.

leukocyte immunoglobulin like receptor B1 (CD85j)

Contents:

References

How to cite this page