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Publication : Early TCRalpha expression generates TCRalphagamma complexes that signal the DN-to-DP transition and impair development.

First Author  Erman B Year  2002
Journal  Nat Immunol Volume  3
Issue  6 Pages  564-9
PubMed ID  12021779 Mgi Jnum  J:76772
Mgi Id  MGI:2180260 Doi  10.1038/ni800
Citation  Erman B, et al. (2002) Early TCRalpha expression generates TCRalphagamma complexes that signal the DN-to-DP transition and impair development. Nat Immunol 3(6):564-9
abstractText  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 TCRalphagamma 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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