HLA-G modulates immune responses by diverse receptor interactions

HLA-G regulates immune responses as it binds different receptors expressed on natural killer (NK) cells, T cells and myeloid cells. HLA-G1 can inhibit NK- and T-cell-mediated lysis of target cells by its interaction with the inhibitory receptors ILT2 and ILT4. Engaging KIR2DL4 triggers different reactions depending on the activation state of the effector cells. The indirect recognition of HLA-G as peptide presented by HLA-E and recognized by the CD94/NKG2 receptor family might further power the battle between the immune system and tumor cells. Secreted HLA-G5 can also bind CD8 and induces Fas/Fas ligand-mediated apoptosis in activated CD8+ lymphocytes.