In-frame TCR delta gene rearrangements play a critical role in the alpha beta/gamma delta T cell lineage decision.
Using a quantitative multiprobe Southern blot analysis, we demonstrate the surprising result that a significant proportion of alpha beta T cells and thymocytes retain T cell receptor delta locus sequences. A substantial portion of the retained delta locus is in a fully V-to-D-to-J rearranged configuration and 20% of these delta rearrangements are functional, significantly less than the 33% predicted for random gene rearrangements. Our observations are in conflict with the idea that alpha beta and gamma delta T cells derive from distinct precursors and suggest that commitment of a common precursor to the gamma delta lineage depends upon expression of a gamma delta T cell receptor. We propose that the intrathymic T cell lineage decision is determined by a competition between the production of functional gamma delta and beta-pre-T cell receptor complexes.
Livak
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Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
Petrie
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HT
Crispe
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Schatz
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DG
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta