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immunoglobulin like domain containing receptor 2

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2986

Nomenclature: immunoglobulin like domain containing receptor 2

Abbreviated Name: ILDR2

Family: Other immune checkpoint proteins

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 639 1q24.1 ILDR2 immunoglobulin like domain containing receptor 2
Mouse 1 661 1 H2.3; 1 73.61 cM Ildr2 immunoglobulin-like domain containing receptor 2
Rat - - 13q23 Ildr2 immunoglobulin-like domain containing receptor 2
Previous and Unofficial Names Click here for help
immunoglobulin-like domain containing receptor 2 | LISCH-like (mouse)
Database Links Click here for help
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Immunopharmacology Comments
ILDR2 has been identified as a novel inhibitory T cell immune checkpoint protein that belongs to the B7-like protein family [2]. It exhibits negative regulatory effects on human and mouse T cells in a number of experimental systems. Its counterpart receptor expressed on activated T cells has not been definitively identified. ILDR2 expression in increased in patient-derived inflamed tissues (samples from ulcerative colitis and Crohn's disease patients). An ILDR2-Fc fusion protein ameliorates disease markers of rheumatoid arthritis in the collagen-induced arthritis mouse model, and in the multiple sclerosis EAE model [6] indicating the potential for pharmacological intervention at this novel immune checkpoint. Bayer are developing their anti-ILDR2 antibody BAY1905254 for immuno-oncology potential (see Phase 1 study NCT03666273). BAY1905254 enhances antigen-specific T cell proliferation and cytotoxicity, and anti-tumour activity has been observed in preclinical studies [4].
General Comments
ILDR2 is one of a family of three 'angulin' proteins [5]: angulin-1 (LSR), angulin-2 (ILDR1) and angulin-3 (ILDR2). The angulins are involved in tricellulin recruitment and formation of tricellular tight-gap junctions that are important to the maintenance of epithelial barrier integrity [1,3,7-8].


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1. Furuse M, Izumi Y, Oda Y, Higashi T, Iwamoto N. (2014) Molecular organization of tricellular tight junctions. Tissue Barriers, 2: e28960. [PMID:25097825]

2. Hecht I, Toporik A, Podojil JR, Vaknin I, Cojocaru G, Oren A, Aizman E, Liang SC, Leung L, Dicken Y et al.. (2018) ILDR2 Is a Novel B7-like Protein That Negatively Regulates T Cell Responses. J Immunol, 200 (6): 2025-2037. [PMID:29431694]

3. Higashi T, Tokuda S, Kitajiri S, Masuda S, Nakamura H, Oda Y, Furuse M. (2013) Analysis of the 'angulin' proteins LSR, ILDR1 and ILDR2--tricellulin recruitment, epithelial barrier function and implication in deafness pathogenesis. J Cell Sci, 126 (Pt 4): 966-77. [PMID:23239027]

4. Huetter J, Gritzan U, Gutcher I, Golfier S, Doecke W-D, Leutke-Eversloh MV, Roider H, Hunter J, Pow A, Liang S et al.. (2018) Abstract 2778: Discovery and preclinical characterization of BAY 1905254 a novel immune checkpoint inhibitor for cancer immunotherapy targeting the immunoglobulin-like domain containing receptor 2 (ILDR2). Cancer Research, 78 (13 (Supplement)). DOI: 10.1158/1538-7445.AM2018-2778

5. Liu Y, Nie H, Liu C, Zhai X, Sang Q, Wang Y, Shi D, Wang L, Xu Z. (2017) Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1. Sci Rep, 7 (1): 7466. [PMID:28785060]

6. Podojil JR, Hecht I, Chiang MY, Vaknin I, Barbiro I, Novik A, Neria E, Rotman G, Miller SD. (2018) ILDR2-Fc Is a Novel Regulator of Immune Homeostasis and Inducer of Antigen-Specific Immune Tolerance. J Immunol, 200 (6): 2013-2024. [PMID:29431690]

7. Sohet F, Lin C, Munji RN, Lee SY, Ruderisch N, Soung A, Arnold TD, Derugin N, Vexler ZS, Yen FT et al.. (2015) LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation. J Cell Biol, 208 (6): 703-11. [PMID:25753034]

8. Watanabe K, Watson E, Cremona ML, Millings EJ, Lefkowitch JH, Fischer SG, LeDuc CA, Leibel RL. (2013) ILDR2: an endoplasmic reticulum resident molecule mediating hepatic lipid homeostasis. PLoS ONE, 8 (6): e67234. [PMID:23826244]

How to cite this page

Other immune checkpoint proteins: immunoglobulin like domain containing receptor 2. Last modified on 04/04/2019. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY,