Perceiving the avidity of T cell activation can be translated into peripheral T cell regulation.

Weiling Chen, Linging Zhang, Bitao Liang, Yvonne Saenger, Jianfeng Li, Leonard Chess, Hong Jiang

Proceedings of the National Academy of Sciences of the United States of America 2007 Dec 18

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The structure recognized by regulatory T cells that enables them to discriminate self from nonself in the periphery is one of the central issues of regulatory T cell biology. A link between immunoregulation and self-nonself discrimination has emerged from experiments showing that Qa-1-restricted CD8(+) T cells selectively down-regulate target T cells activated by the intermediate avidity of their own T cell antigen receptor-ligand interactions. Because the peripheral self-reactive T cell repertoire is devoid of high-avidity T cells compared with the foreign-reactive repertoire, as a result of thymic negative selection, the selective down-regulation of intermediate but not high-avidity T cells enables the immune system to suppress autoimmunity without damaging the ongoing immune response to foreign pathogens. However, the molecular mechanism delineating how avidity of T cell activation is perceived by the regulatory T cells has not been elucidated. Here we show that a heat shock peptide (Hsp60sp), coupled with the MHC class Ib molecule Qa-1, is a surrogate target structure that is preferentially expressed at a higher level on the intermediate avidity T cells and specifically recognized by the Qa-1-restricted CD8(+) T cells. The biological significance of this observation was confirmed by the ability of Hsp60sp-loaded relevant dendritic cells to induce a Qa-1-restricted CD8(+) T cell-mediated protection from autoimmune encephalopathy in the experimental allergic encephalomyelitis model. Thus, perceiving the avidity of T cell activation can be translated into peripheral T cell regulation to discriminate self from nonself in the periphery to maintain self-tolerance.

Citation

Weiling Chen, Linging Zhang, Bitao Liang, Yvonne Saenger, Jianfeng Li, Leonard Chess, Hong Jiang. Perceiving the avidity of T cell activation can be translated into peripheral T cell regulation. Proceedings of the National Academy of Sciences of the United States of America. 2007 Dec 18;104(51):20472-7