HLA-G and LILRBs

the new targets for first-in-class drug discovery

 
 
 

MHC class I (major histocompatibility complex-I) polymorphisms are associated with the outcome of some viral infections and autoimmune diseases. MHC-I proteins present antigenic peptides and are recognized by receptors, thus enabling the immune system to detect self-antigens and eliminate targets lacking self or expressing foreign antigens. Human leukocyte antigen G (HLA-G) is a non-classical human MHC class Ib molecule, which is an important immune tolerance molecule in the body, contributing to immune escape or immune cell anergy. In recent years, it has been regarded as a new type of immune checkpoint.

HLA-G, like other immune checkpionts, mediates its function by binding to receptors on immune cells. The known receptors are leukocyte Ig-like receptor subfamily B member 1 (LILRB1) and member 2 (LILRB2) which belong to the Leukocyte Ig-like receptor (LILR) family. LILRs is one kind of these receptors that either activate (LILRA members) or suppress (LILRB members) immune cell functions. These Type 1 transmembrane glycoproteins are composed of two or four extracellular Ig-like domains that bind ligands. When HLA-G binds to LILRBs, tumor cells can escape the surveillance of the immune system. As LILRBs have a similar immunoreceptor tyrosine-based inhibitory motif (ITIM) like immune checkpoint proteins such as CTLA4 and PD-1 (Fig. 1), they became hot targets for drug development, especially used for discovery of first-in-class drugs. Multiple clinical/preclinical studies showed the potential broad anti-tumor effects of LILR family proteins, such as BND-22 (Biond), IO-202 (Immune Onc), JTX-8064 (Jounce Therapeutics) and NC410 (NextCure). In addition, since the expression profile of HLA-G is significantly different from that of PD-L1, it is suggested that HLA-G antibodies can enhance tumor sensitivity to anti-PD-L1 therapy in patients with tumors that do not respond to anti-PD-L1 therapy.

 

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Fig. 1 LILRBs binding ligands.
Based on our featured SAMSTM platform, Kactus has developed a series of proteins/domains in LILR family. As LILRB1 and LILRB2 preferentially binds to HLA-G for MHC-I binding, we also developed multiple forms of HLA-G complex for further applications.
Advantages
  • Exclusively available in various forms of HLA-G
  • Provides the HLA-G binding domain of LILRBs
  • Developed blocking analysis method for LILRBs and HLA-G binding
  • Multiple activity assays
Our Data

Human LILRB2 / CD85d / ILT4 LILRB2 Domain1&2 Protein

ELISA Data

 

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SPR Data

 

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Human HLA-G Complex Tetramer, His Tag immobilized on CM5 Chip can bind Human LILRB2 Domain1&2, His Tag with an affinity constant of 6.5μM as determined in a SPR assay (Biacore T200)

Human LILRB2 / CD85d / ILT4 Protein

ELISA Data

 

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SPR Data

 

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Human LILRB2 captured on Protein A Chip can bind HLA-G Complex Tetramer, His Tag with an affinity constant of 9.2 nM as determined in SPR assay (Biacore T200).
Product List
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Cat. No. Protein Name Species Tag Exp. System  
hot.pngHLG-HE41F Human HLA-G Free Heavy Chain Protein Human C-His-Avi E.coli Inquiry Now
hot.pngHLG-HM41C Human HLA-G Complex Protein Human C-His-Avi Expi293 Inquiry Now
hot.pngHLG-HM41CB Biotinylated Human HLA-G Complex Protein Human C-His-Avi Expi293 Inquiry Now
hot.pngHLG-HM41CT Human HLA-G Complex Tetramer Protein Human C-His-Avi Expi293 Inquiry Now
hot.pngHLG-HM41CTB Biotinylated Human HLA-G Complex Tetramer Protein Human C-His-Avi Expi293 Inquiry Now
hot.pngHLG-RM41CT Rhesus macaque HLA-G Complex Tetramer Protein Rhesus macaque C-His-Avi Expi293 Inquiry Now
hot.pngHLG-CM41CT Cynomolgus HLA-G Complex Tetramer Protein Cynomolgus C-His-Avi Expi293 Inquiry Now
LIL-HM4A1 Human LILRA1/CD85i/LIR-6 Protein Human C-His-Avi Expi293 Inquiry Now
LIL-HM4A2 Human LILRA2/CD85h/ILT1 Protein Human C-His-Avi Expi293 Inquiry Now
LIL-HM4A3 Human LILRA3/CD85e Protein Human C-His-Avi Expi293 Inquiry Now
LIL-HM4A4 Human LILRA4/CD85g Protein Human C-His-Avi Expi293 Inquiry Now
LIL-CM1A4 Cynomolgus LILRA4/CD85g Protein Cynomolgus C-His Expi293 Inquiry Now
LIL-HM4A5 Human LILRA5/CD85f/ILT11 Protein Human C-His-Avi Expi293 Inquiry Now
LIL-HM4A6 Human LILRA6/CD85b/ILT8 Protein Human C-His-Avi Expi293 Inquiry Now
LIL-HM4B1 Human LILRB1/CD85j/ILT2 Protein Human C-His-Avi Expi293 Inquiry Now
LIL-HM2B1 Human LILRB1/CD85j/ILT2 Protein Human C-hFc Expi293 Inquiry Now
LIL-CM1B1 Rhesus macaque LILRB1/CD85j/ILT2 Protein Rhesus macaque C-His Expi293 Inquiry Now
LIL-HM11D Human LILRB1/CD85j/ILT2 Domain1&2 Protein Human C-His Expi293 Inquiry Now
LIL-HM4B2 Human LILRB2/CD85d/ILT4 Protein Human C-His-Avi Expi293 Inquiry Now
LIL-HM2B2 Human LILRB2/CD85d/ILT4 Protein Human C-hFc Expi293 Inquiry Now
LIL-HM12D Human LILRB2/CD85d/ILT4 Domain1&2 Protein Human C-His Expi293 Inquiry Now
LIL-CM1B2 Cynomolgus LILRB2/CD85d/ILT4 Protein Cynomolgus C-His Expi293 Inquiry Now
LIL-HM4B3 Human LILRB3/CD85a/ILT5 Protein Human C-His-Avi Expi293 Inquiry Now
LIL-HM4B4 Human LILRB4/CD85k/ILT3 Protein Human C-His-Avi Expi293 Inquiry Now
LIL-HM2B4 Human LILRB4/CD85k/ILT3 Protein Human C-hFc Expi293 Inquiry Now
LIL-MM1B4 Mouse LILRB4/CD85k/ILT3 Protein Mouse C-His Expi293 Inquiry Now
LIL-CM1B4 Cynomolgus LILRB4/CD85k/ILT3 Protein Cynomolgus C-His Expi293 Inquiry Now
LIL-HM4B5 Human LILRB5/CD85c/LIR-8 Protein Human C-His-Avi Expi293 Inquiry Now
ANG-HM4L2 Human ANGPTL2/Angiopoietin-like 2 Protein Human C-His-Avi Expi293 Inquiry Now
ANG-HM403 Human ANGPTL3/Angiopoietin-like 3 Protein Human C-His-Avi Expi293 Inquiry Now
ANG-HM1L4 Human ANGPTL4/Angiopoietin-like 4 Protein Human N-His Expi293 Inquiry Now
ANG-HM1L4 Human ANGPTL4/Angiopoietin-like 4 Protein Human N-His Expi293 Inquiry Now
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