Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) – Human leukocyte antigen (HLA) class I complex (LILRB1–HLA class I)

The LILRB1–HLA class I complex represents a critical inhibitory immune checkpoint interaction between the Leukocyte Immunoglobulin-Like Receptor B1 (LILRB1) and various Human Leukocyte Antigen (HLA) class I molecules, including HLA-A, HLA-B, and notably the non-classical HLA-G. LILRB1 is expressed on the surface of various immune cells, including Natural Killer (NK) cells, B cells, monocytes, and subsets of T cells, where it transmits inhibitory signals via its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) upon binding to its ligands. In the context of oncology, many tumors overexpress HLA class I molecules (particularly HLA-G) to exploit this pathway, effectively 'switching off' the immune system's ability to recognize and destroy malignant cells. Therapeutic strategies targeting this interaction primarily involve monoclonal antibodies designed to block LILRB1, thereby preventing the inhibitory signal and reinvigorating the effector functions of NK and T cells against the tumor. Beyond cancer, this axis is also implicated in viral evasion strategies, where certain viruses, such as cytomegalovirus (CMV), produce HLA class I mimics to trigger LILRB1 and suppress the host immune response.

Other names

LIR-1CD85jILT2MIR-7Leukocyte immunoglobulin-like receptor 1Immunoglobulin-like transcript 2Monocyte/macrophage immunoglobulin-like receptor 7HLA-G receptor

Antagonist antibody that blocks the interaction between LILRB1 and HLA class I molecules to prevent inhibitory signaling and restore the anti-tumor activity of NK cells and T cells.