Crucial function of the pre-T-cell receptor (TCR) in TCRP selection, TCRβ allelic exclusion and αβ versus γδ lineage commitment |
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Authors: | Harald von Boehmer Iannis Aifantis Orly Azogui Jacqueline Feinberg Claude Saint-Ruf Carole Zober Corinne Garcia Jan Buer |
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Institution: | Inscitut Necker, INSERM U373, Facultéde Médecine, Necker-Enfants-Malades, Paris, France. |
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Abstract: | Summary: The analysis of T-cell receptor (TCR) βselection, TCRβ allelic exclusion and TCRβ rearrangement in γδ T cells from normal and pre-TCR-deficient mice has shown that the pre-TCR has a crucial role in T-lyinpbocyte development: - *
The pre-TCR is by far the most effective receptor that generates large numbers of CD4+8+ T cells with productive TCRβ rearrangements. - *
In the absence of the pre-TCR, TCRβ rearrangement proceeds in developing cells irrespective of whether they already contain a productive TCRβ gene. - *
The pre-TCR directs developing T cells to the αβ lineage because y5 T cells from pTα-/- mice proceed much further in TCRβ rearrangement than γδ T cells from wild-type mice. It is argued that the pre-TCR commits developing T cells to the αβ lineage by an instructive mechanism, which has largely replaced an evolutionarily more ancient mechanism that involves stochastic αβ lineage commitment.
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