ArticleProceedings of the National Academy of Sciences of the United States of America2007
Perceiving the avidity of T cell activation can be translated into peripheral T cell regulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Novel Autologous Dendritic Cell Therapy AVT001 for Type 1 Diabetes.NEJM evidence · 2024Trial
- CD8+ Regulatory T Cells.Annual review of immunology · 2026Review
- Towards Clinical Translation of CD8International journal of molecular sciences · 2019Review
- PFA-fixed Hsp60sp-loaded dendritic cells as a vaccine for the control of mouse experimental allergic encephalomyelitis.Cellular & molecular immunology · 2014Article
- CD8+ regulatory T cells induced by T cell vaccination protect against autoimmune nephritis.Journal of the American Society of Nephrology : JASN · 2012Article
- An MHC class Ib-restricted CD8+ T cell response to lymphocytic choriomeningitis virus.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- CD8(+) Tregs in autoimmunity: learning "self"-control from experience.Cellular and molecular life sciences : CMLS · 2011Review
- Regulation of self-tolerance by Qa-1-restricted CD8(+) regulatory T cells.Seminars in immunology · 2011Review
- Pathogenic and regulatory T cells in type 1 diabetes: losing self-control, restoring it, and how to take the temperature.Current diabetes reports · 2011Review
- Diverse roles of non-diverse molecules: MHC class Ib molecules in host defense and control of autoimmunity.Current opinion in immunology · 2011Review
- Antigen-specific splenic CD4+ and CD8+ regulatory T cells generated via the eye, suppress experimental autoimmune encephalomyelitis either at the priming or at the effector phase.International immunology · 2011Article
- Comeback kids: CD8(+) suppressor T cells are back in the game.The Journal of clinical investigation · 2010Article
- HLA-E-restricted regulatory CD8(+) T cells are involved in development and control of human autoimmune type 1 diabetes.The Journal of clinical investigation · 2010Article
- Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance.Nature · 2010Article
- Commensal microbiota and CD8+ T cells shape the formation of invariant NKT cells.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- The specificity of T cell regulation that enables self-nonself discrimination in the periphery.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Regulation of CD8+ regulatory T cells: Interruption of the NKG2A-Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.