Regulation of self-tolerance by Qa-1-restricted CD8(+) regulatory T cells - PubMed (original) (raw)

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Regulation of self-tolerance by Qa-1-restricted CD8(+) regulatory T cells

Hye-Jung Kim et al. Semin Immunol. 2011 Dec.

Abstract

Mounting an efficient immune response to pathogens while avoiding damage to host tissues is the central task of the immune system. Emerging evidence has highlighted the contribution of the CD8(+) lineage of regulatory T cells to the maintenance of self-tolerance. Specific recognition of the MHC class Ib molecule Qa-1 complexed to peptides expressed by activated CD4(+) T cells by regulatory CD8(+) T cells triggers an inhibitory interaction that prevents autoimmune responses. Conversely, defective Qa-1-restricted CD8(+) regulatory activity can result in development of systemic autoimmune disease. Here, we review recent research into the cellular and molecular basis of these regulatory T cells, their mechanism of suppressive activity and the potential application of these insights into new treatments for autoimmune disease and cancer.

Copyright © 2011. Published by Elsevier Ltd.

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Figures

Fig. 1

Dual binding activity of Qa-1 and generation of Qa-1 mutant mice. (A) Engagement of Qa-1 with NKG2A/CD94 and TCR delivers opposing signal. (B) Lack of two opposing signals in Qa-1 deficient mice results in compensated phenotype. (C) Qa-1 D227K mutation leads to the interruption of TCR and Qa-1–peptide binding that leads to the lack of CD8+ Treg activity. Qa-1 D227K mice develop lupus-like autoimmune disorder.

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