Figure 8. Summary of functional effects of MICA-129 variants depending on expression intensity.

1. For target cells expressing the MICA-129Val variant, the degree of NK-cell cytotoxicity and IFNγ production increased steadily with the MICA expression intensity. Augmented expression of the high-avidity MICA-129Met isoform, in contrast, had no or even a negative effect on these NK-cell functions due to a rapid down-regulation of NKG2D on NK cells.
2. 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.