Regulation of CD8+ regulatory T cells: Interruption of the NKG2A–Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease
Proceedings of the National Academy of Sciences, 2008•National Acad Sciences
Regulation of autoreactive CD4 T cells is essential to maintain self-tolerance and prevent
autoimmune disease. Although CD8 T regulatory (Treg) cells that recognize self-peptides
restricted by Qa-1 (HLA-E in humans) inhibit autoreactive CD4 cells and attenuate
experimental autoimmune encephalomyelitis (EAE), the mechanism of this interaction is
unclear. We generated Qa-1 mutant knock-in mice that impair Qa-1 binding to the T cell
receptor (TCR) and CD94/NKG2A receptors. Analysis of these mice showed that TCR …
autoimmune disease. Although CD8 T regulatory (Treg) cells that recognize self-peptides
restricted by Qa-1 (HLA-E in humans) inhibit autoreactive CD4 cells and attenuate
experimental autoimmune encephalomyelitis (EAE), the mechanism of this interaction is
unclear. We generated Qa-1 mutant knock-in mice that impair Qa-1 binding to the T cell
receptor (TCR) and CD94/NKG2A receptors. Analysis of these mice showed that TCR …
Regulation of autoreactive CD4 T cells is essential to maintain self-tolerance and prevent autoimmune disease. Although CD8 T regulatory (Treg) cells that recognize self-peptides restricted by Qa-1 (HLA-E in humans) inhibit autoreactive CD4 cells and attenuate experimental autoimmune encephalomyelitis (EAE), the mechanism of this interaction is unclear. We generated Qa-1 mutant knock-in mice that impair Qa-1 binding to the T cell receptor (TCR) and CD94/NKG2A receptors. Analysis of these mice showed that TCR-dependent recognition of Qa-1–peptide complexes on target CD4 cells is essential for suppression by CD8 Treg cells. Further analysis revealed that genetic disruption of the Qa-1–CD94/NKG2A interaction unleashes robust CD8 Treg cell activity that completely abolishes development of EAE.
National Acad Sciences