The cell biology of the human natural killer cell CD94/NKG2A inhibitory receptor

To avoid destruction of normal bystander cells, natural killer (NK) cells must provide a continuous supply of functional inhibitory receptors to their cell surface. After interaction with its ligand HLA-E, which is expressed on normal cells, the C-type lectin inhibitory receptor CD94/NKG2A suppresses activation signaling processes. CD94/NKG2A receptors continuously recycle from the cell surface through endosomal compartments and back again in a process that requires energy and the cytoskeleton. This steady state process appears to be largely unaffected by exposure to ligand. CD94/NKG2A receptors move freely within the plasma membrane and accumulate at the site of contact with the ligand bearing target cells (or monoclonal antibodies (mAb) coated beads). As expected, ligated CD94/NKG2A receptors are less mobile than the nonligated receptors, and the lipid raft marker cholera toxin B is excluded from the CD94/NKG2A enriched target cell contact sites. Also, methylcyclodextrin does not interfere with CD94/NKG2A accumulation at these contact sites. The constant renewal of CD94/NKG2A receptors at the cell surface and their free mobility within the plasma membrane likely facilitates and insures inhibitory capacity.