leukocyte immunoglobulin like receptor B1 (CD85j)

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:

Immuno Process:

Immuno Process:

Immuno Process:

Immuno Process:

Immuno Process:

Immune system development

Immuno Process:

Cytokine production & signalling

Immuno Process:

Chemotaxis & migration

Immuno Process:

Cellular signalling

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

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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 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2973.

leukocyte immunoglobulin like receptor B1 (CD85j)

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References

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