HLA-E and infection: Mechanistically, impaired NKG2C+ NK cell responses in MS have been linked to the absence of HCMV infection, a genetic deletion of the NKG2C receptor—which directly correlates with reduced or absent NKG2C surface levels and decreased frequency of NKG2C+ NK cells in vivo (138, 139)—or infection with HCMV isolates encoding UL40 peptide variants that induce only weak HLA-E upregulation and limited expansion of NKG2C+ NK cells.