The mouse protein Qa-1 (HLA-E in humans) is essential for immunological protection and immune regulation. Although Qa-1 has been linked to CD8 T cell–dependent suppression, the physiological relevance of this observation is unclear. We generated mice deficient in Qa-1 to develop an understanding of this process. Qa-1-deficient mice develop exaggerated secondary CD4 responses to foreign and self peptides. Enhanced responses to proteolipid protein self peptide were associated with resistance of Qa-1-deficient CD4 T cells to Qa-1-restricted CD8 T suppressor activity and increased susceptibility to experimental autoimmune encephalomyelitis. These findings delineate a Qa-1-dependent T cell–T cell inhibitory interaction that prevents the pathogenic expansion of autoreactive CD4 T cell populations and consequent autoimmune disease.
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We thank J. Horner and R.A. DePinho (Dana Farber Cancer Institute) and A. Sharpe (Brigham and Women's Hospital) for the expertise provided by their transgenic mouse facilities; S. Kissler for technical advice and assistance; and A. Angel for assistance with preparation of the manuscript and figures. Supported in part by National Institutes of Health (AI 13600, AI37562 and AI 48125 to H.C.; and AI 07386 to D.H.).
The authors declare no competing financial interests.
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Hu, D., Ikizawa, K., Lu, L. et al. Analysis of regulatory CD8 T cells in Qa-1-deficient mice. Nat Immunol 5, 516–523 (2004). https://doi.org/10.1038/ni1063
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