Major Histocompatibility Complex, Class I, C (HLA-C) group 1 (HLA-C1)

HLA-C group 1 (HLA-C1) ligands are a specific subset of Major Histocompatibility Complex (MHC) class I molecules defined by the presence of an asparagine residue at position 80 of the alpha-1 domain (Hilton et al., 2015, Journal of Immunology). These molecules are expressed on the surface of most nucleated cells and function as the primary ligands for the inhibitory Killer Cell Immunoglobulin-like Receptors KIR2DL2 and KIR2DL3, which are predominantly found on Natural Killer (NK) cells (Parham, 2005, Nature Reviews Immunology). The interaction between HLA-C1 and these receptors is a critical immune checkpoint that maintains self-tolerance by delivering inhibitory signals that prevent NK cell-mediated lysis of healthy cells. However, many tumors exploit this pathway by maintaining or upregulating HLA-C1 expression to evade immune detection. Therapeutic strategies, such as the development of monoclonal antibodies like lirilumab, aim to block the KIR2DL2/3 receptors from binding to HLA-C1, thereby releasing the brakes on NK cells to promote anti-tumor activity (Benson et al., 2012, Blood). Additionally, the genetic diversity of HLA-C1 and its KIR receptors is linked to susceptibility to viral infections, autoimmune diseases, and complications during pregnancy such as preeclampsia (Moffett & Colucci, 2014, Nature Reviews Immunology). Understanding the HLA-C1/KIR axis is essential for developing personalized immunotherapies that leverage the innate immune system.

Other names

HLA-C Asn80MHC class I antigen C group 1HLA-C1 ligandsC1 epitopeHLA-Cw1HLA-Cw3HLA-Cw7HLA-Cw8HLA-Cw12HLA-Cw14HLA-Cw16

Checkpoint inhibition by blocking the interaction between inhibitory KIR2DL2/3 receptors and HLA-C1 ligands to prevent inhibitory signaling and enhance Natural Killer (NK) cell-mediated cytotoxicity.