HLA-G and LILR Proteins
Unlock the Potential of First-in-Class Drug Discovery with Recombinant HLA-G and LILR Products
Novel Combination of Targets in Immune Response and Drug Discovery
Leukocyte Immunoglobulin-Like Receptors (LILRs) are a family of receptors primarily expressed on immune cells, playing critical roles in modulating immune responses. They are type I transmembrane glycoproteins characterized by the presence of extracellular immunoglobulin-like domains. LILRs can be activating (LILRAs) or inhibitory (LILRBs), with the inhibitory receptors possessing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic tails. These receptors recognize a variety of ligands, including major histocompatibility complex (MHC) class I molecules, and their interaction with these ligands can influence the function of various immune cells, including dendritic cells, macrophages, and T and B lymphocytes.
Through these interactions, LILRs contribute to the regulation of both innate and adaptive immune responses, playing roles in immune tolerance, inflammation, and the defense against pathogens. Their dysregulation has also been implicated in various diseases, including autoimmune conditions, cancer, and infectious diseases. This highlighting their importance in immune homeostasis and their potential as therapeutic targets.
Figure 1. LILRB binding ligands.
MHC-I proteins present antigenic peptides and are recognized by associated receptors. This enables the immune system to detect self-antigens and eliminate targets lacking self-antigens or expressing foreign antigens. Human leukocyte antigen G (HLA-G) is a non-classical human MHC class Ib molecule. It 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 checkpoints, mediates its function by binding to receptors on immune cells. The known receptors of HLA-G 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 are one kind of these receptors that either activates (LILRA members) or suppresses (LILRB members) immune cell functions. 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, they've become hot targets for drug development, especially for discovery of first-in-class drugs.
Multiple clinical/preclinical studies show 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, HLA-G antibodies might be able to enhance tumor sensitivity to anti-PD-L1 therapy. This would be a novel breakthrough for patients with tumors that do not respond to anti-PD-L1 therapy.
Figure 2. Human LILRB2, hFc Tag captured on CM5 Chip via Protein A can bind Human HLA-G&B2M&Peptide (RIIPRHLQL) Tetramer with an affinity constant of 4.62 nM as determined in SPR assay (Biacore T200).
Figure 4. Cynomolgus LILRB2, His Tag immobilized on CM5 Chip can bind Cynomolgus HLA-G Complex Tetramer, His Tag with an affinity constant of 852 nM as determined in SPR assay (Biacore T200).
Figure 3. Rhesus macaque LILRB1, hFc Tag captured on CM5 Chip via Protein A can bind Rhesus macaque HLA-G&B2M&Peptide (RIIPRHLQL) Tetramer, His Tag with an affinity constant of 1.74 nM as determined in SPR assay (Biacore T200).
Figure 5. Serial dilutions of Anti-LILRB2 Antibody were added into Human LILRB2, His Tag : Biotinylated HLA-G Complex Tetramer, His Tag binding reactioins. The half maximal inhibitiory concentration (IC50) is 75.3ng/ml.
KACTUS has developed a full portfolio of mammalian-expressed HLA-G monomers and tetramers including biotinylated versions. Our HLA-G monomers and tetramers are mammalian-expressed from HEK293 cells and have >95% purity with low endotoxin (<1EU/ug). HLA-G monomers and tetramers can be used for antibody discovery, TCR binding, and flow cytometry. We also offer custom HLA-G tetramers. Contact us today to learn more.
LILRA, LILRB, and APOE Products
Using our SAMS protein engineering platform, we have developed a large portfolio of LILRA and LILRB catalog products. These products are expressed from HEK293 cells and are available in multiple species, including human, mouse, cynomolgus, and rhesus macaque as well as biotinylated versions. Contact us today to request a custom LILR.
Additional MHC Products/Services
Load your own antigenic peptide onto an MHC monomer or tetramer.
Soluble TCR Expression
Custom expression of soluble TCR with TCR/MHC binding analysis via SPR
MHC Peptide Complexes
MHC peptide complexes with class I or II alleles and catalog or custom peptides.