Figure 2. Immunological mechanisms of HLA-E-mediated immunosuppression by cancer cells. In Cancer cells expose HLA-G (in green) and HLA-E (in red) molecules of their surface. The secretion of HLA-E induces apoptosis in immune effectors. Moreover, in the presence of interferon γ (IFNγ), HLA-G and HLA-E molecules are expressed at increased levels on the surface of both cancer cells and CD4⁺ T lymphocytes. The binding of HLA-E expressed on CD4⁺ T cells to the T-cell receptor (TCR) of CD4⁺ T lymphocytes can induce the differentiation of the latter into regulatory CD8⁺ T cells (CD8⁺ reg). The binding of HLA-E to NKG2A inhibits the cytotoxic functions of CD8⁺ T lymphocytes and NK cells.