Immune self-tolerance and prevention of autoimmune disease relies on the regulation of autoreactive CD4 T cells. CD8 cells that recognize the MHC class Ib molecule Qa-1 (known as HLA-E in humans) can suppress autoimmune disease in an animal model of multiple sclerosis, the experimental autoimmune encephalitis (EAE) mouse. However, the mechanism of Qa-1 function is unknown. Thus, Lu et al. generated knock-in mice with a mutated form of Qa-1, which lacks the ability to bind to either the CD4 T cell receptor or the CD94/NKG2A receptor that is expressed on CD8 and natural killer cells. They found that disruption of the Qa-1–NKG2A interaction caused potent activation of CD8 T regulatory cells, resulting in a halt in disease development in these mice. This study highlights a potential therapy for autoimmune diseases, such as multiple sclerosis, by inducing CD8 activity through a molecular block of the Qa-1–NKG2A interaction.

Lu L., Kim H.-J., Werneck M.B.F., Cantor H. (2008). Regulation of CD8+ regulatory T cells: interruption of the NKG2A–Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease. Proc. Natl. Acad. Sci. 105, 19420– 19425.
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2009