leukocyte immunoglobulin like receptor B1 (CD85j) | Other immune checkpoint proteins | IUPHAR/BPS Guide to PHARMACOLOGY

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leukocyte immunoglobulin like receptor B1 (CD85j)

target has curated data in GtoImmuPdb

Target id: 2973

Nomenclature: leukocyte immunoglobulin like receptor B1 (CD85j)

Abbreviated Name: LILRB1

Family: Other immune checkpoint proteins, 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 1 650 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
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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
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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 15 GO processes
GO:0001915 negative regulation of T cell mediated cytotoxicity IDA
GO:0002230 positive regulation of defense response to virus by host IDA
GO:0002740 negative regulation of cytokine secretion 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:0050776 regulation of immune response TAS
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 3 GO processes
GO:0097028 dendritic cell differentiation IEP
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 11 GO processes
GO:0002740 negative regulation of cytokine secretion involved in immune response IDA
GO:0032609 interferon-gamma production IDA
GO:0032689 negative regulation of interferon-gamma production IDA
GO:0035548 negative regulation of interferon-beta secretion IDA
GO:0042536 negative regulation of tumor necrosis factor biosynthetic process IDA
GO:0045077 negative regulation of interferon-gamma biosynthetic process IDA
GO:0060907 positive regulation of macrophage cytokine production IDA
GO:0072643 interferon-gamma secretion IDA
GO:2001180 negative regulation of interleukin-10 secretion IDA
GO:2001183 negative regulation of interleukin-12 secretion IDA
GO:2001202 negative regulation of transforming growth factor-beta secretion 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: 
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.

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

Other immune checkpoint proteins: leukocyte immunoglobulin like receptor B1 (CD85j). Last modified on 15/05/2018. Accessed on 23/10/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2973.