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Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes

Author

Listed:
  • Irena Stefanová

    (National Institutes of Health)

  • Jeffrey R. Dorfman

    (National Institutes of Health
    Kenya Medical Research Institute, Wellcome Trust Research Laboratories)

  • Ronald N. Germain

    (National Institutes of Health)

Abstract

Major histocompatibility complex (MHC) class I and II molecules are highly polymorphic proteins that bind and present foreign peptides to the clonally distributed αβ receptors (TCR) of T lymphocytes. As a population, the immature T lymphocytes generated in the thymus express a very diverse set of TCR specificities. A process of positive selection filters this broad repertoire to optimize peripheral T cells for antigen recognition in the context of available MHC products. Only those precursor T cells whose TCRs generate an adequate but not excessive signalling response to self-peptides bound to the expressed MHC proteins undergo successful maturation1. Here we show that post-thymic self-recognition facilitates the antigen reactivity of mature T cells. Both experimental and physiological interruption of T-cell contact with self-peptide MHC ligands leads to a rapid decline in signalling and response sensitivity to foreign stimuli. Because the adaptive immune system must be recruited early in an infectious process when antigen is limiting2, these findings suggest that positive selection ensures predictable T-cell recognition of available self-ligands, which in turn promotes efficient responses to pathogens.

Suggested Citation

  • Irena Stefanová & Jeffrey R. Dorfman & Ronald N. Germain, 2002. "Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes," Nature, Nature, vol. 420(6914), pages 429-434, November.
  • Handle: RePEc:nat:nature:v:420:y:2002:i:6914:d:10.1038_nature01146
    DOI: 10.1038/nature01146
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    Cited by:

    1. Farzad Fatehi & Yuliya N. Kyrychko & Konstantin B. Blyuss, 2018. "Effects of Viral and Cytokine Delays on Dynamics of Autoimmunity," Mathematics, MDPI, vol. 6(5), pages 1-24, April.

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