Regulation of CD8+ regulatory T cells: Interruption of the NKG2A-Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 19047627.
- Also identified by DOI 10.1073/pnas.0810383105 and PMC identifier 2614776.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
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.
Medical subject headings
- CD8-Positive T-Lymphocytes
- Encephalomyelitis, Autoimmune, Experimental
- Histocompatibility Antigens Class I
- NK Cell Lectin-Like Receptor Subfamily C
- T-Lymphocytes, Regulatory