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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Autoimmunity / immunology
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CD8-Positive T-Lymphocytes / immunology*
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Gene Knock-In Techniques
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / immunology*
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Histocompatibility Antigens Class I / metabolism
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Immune Tolerance / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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NK Cell Lectin-Like Receptor Subfamily C / genetics
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NK Cell Lectin-Like Receptor Subfamily C / immunology*
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NK Cell Lectin-Like Receptor Subfamily C / metabolism
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NK Cell Lectin-Like Receptor Subfamily D / immunology
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NK Cell Lectin-Like Receptor Subfamily D / metabolism
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Perforin / genetics
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Perforin / immunology
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Perforin / metabolism
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T-Lymphocytes, Regulatory / immunology*
Substances
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Histocompatibility Antigens Class I
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NK Cell Lectin-Like Receptor Subfamily C
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NK Cell Lectin-Like Receptor Subfamily D
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Q surface antigens
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Perforin