HLA-G up-regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells

The nonclassical HLA class I antigen HLA-G is an inhibitory molecule involved in immune tolerance and immune escape. HLA-G exerts its inhibitory functions via interaction with inhibitory receptors ILT2, ILT4, and KIR2DL4, differentially expressed by NK, T, and antigen-presenting cells. Cells expressing HLA-G and cells expressing its receptors are often found in the vicinity of each other, but the mechanisms responsible for this colocalization are still unknown. We report that ILT2, ILT3, ILT4, and KIR2DL4 expression is up-regulated by HLA-G in antigen-presenting cells, NK cells, and T cells. Because this up- regulation seems not to require antigenic costimulation, it might precede an immune response. Functionally, up- regulation of inhibitory receptors in immune cells before stimulation might increase their activation thresholds and participate in immune escape mechanisms.