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Early TCR alpha expression generates TCR complexes that signal the DN-to-DP transition and impair development

  1. Author:
    Erman, B.
    Feigenbaum, L.
    Coligan, J. E.
    Singer, A.

  2. Author Address

    NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA Singer A NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA
    1. Year: 2002
  2. Journal: Nature Immunology
    1. 3
    2. 6
    3. Pages: 564-569
  4. Type of Article: Article
  1. Abstract:

    Clonotypic T cell receptor (TCR) genes undergo ordered rearrangement and expression in the thymus with the result that TCRalpha and TCRgamma proteins are not expressed in the same cell at the same time. Such "TCRalpha/gamma exclusion" is a feature of normal thymocyte differentiation, but it is abrogated in TCR-transgenic mice, which prematurely express transgenic TCRalpha proteins in early double-negative (DN) thymocytes. We report here that early expression of TCRalpha proteins results in the formation of TCRalpha/gamma complexes that efficiently signal the differentiation of DN into double- positive thymocytes independently of pre-TCR and TCRbeta expression. Thus, abrogation of TCRalpha/gamma exclusion by early TCRalpha expression results in the formation of isotypically mixed TCRalphagamma complexes whose in vivo signals circumvent TCRbeta selection and redirect thymocyte development along an aberrant developmental pathway.

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