Human leukocyte antigen G and Human leukocyte antigen C (HLA-G, HLA-C)

HLA-G and HLA-C are major histocompatibility complex class I molecules prominently expressed on fetal-derived trophoblast cells at the maternal-fetal interface. HLA-G is a non-classical class I molecule with low polymorphism and unique isoforms, central to immune tolerance during pregnancy, protecting the fetus from maternal immune attack and modulating NK cell activity. HLA-C is a classical class I molecule with a broader peptide repertoire, also expressed on trophoblasts and interacting with maternal NK cells through specific KIRs, regulating tolerance and placental vascular remodeling. Their selective expression in trophoblasts and low expression in most adult tissues underpins their role as immune checkpoints in pregnancy and makes them relevant in therapeutic strategies for immune tolerance and certain pathologies.

Other names

HLA-G: Histocompatibility antigen, class I, GHLA-C: Histocompatibility antigen, class I, CMHC class I G (HLA-G)MHC class I C (HLA-C)non-classical MHC (HLA-G)classical MHC (HLA-C)

For antibody-based drugs: Blockade or modulation of HLA-G/HLA-C can modulate immune recognition, either enhancing immune clearance (immunotherapy in cancer) or inducing tolerance (preventing rejection/pregnancy complications). Soluble forms can act as decoys, modulating immune cell signaling by engaging inhibitory receptors (ILT2/LILRB1, KIR2DL4, etc)