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.