Antigen-dependent co-stimulation of CD8+ T cells with the MICA-129Met variant allowed for an earlier antigen-dependent activation than co-stimulation with the MICA-129Val variant. However, the down-regulation of NKG2D in response to MICA-129Met ligands impaired any subsequent NKG2D-dependent co-stimulation and T-cell activation. The down-regulation of NKG2D on CD8+ T cells was augmented with MICA-129Met expression intensity. 