Premature expression of T cell receptor (TCR)αβ suppresses TCRγδ gene rearrangement but permits development of γδ lineage T cells

The T cell receptor (TCR)gamma delta and the pre-TCR promote survival and maturation of early thymocyte precursors. Whether these receptors also influence gamma delta versus alpha beta lineage determination is less clear. We show here that TCR gamma delta gene rearrangements are suppressed in TCR alpha beta transgenic mice when the TCR alpha beta is expressed early in T cell development. This situation offers the opportunity to examine the outcome of gamma delta versus alpha beta T lineage commitment when only the TCR alpha beta is expressed. We find that precursor thymocytes expressing TCR alpha beta not only mature in the alpha beta pathway as expected, but also as CD4(-)CD8(-) T cells with properties of gamma delta lineage cells. In TCR alpha beta transgenic mice, in which the transgenic receptor is expressed relatively late, TCR gamma delta rearrangements occur normally such that TCR alpha beta(+)CD4(-)CD8(-) cells co-express TCR gamma delta. The results support the notion that TCR alpha beta can substitute for TCR gamma delta to permit a gamma delta lineage choice and maturation in the gamma delta lineage. The findings could fit a model in which lineage commitment is determined before or independent of TCR gene rearrangement. However, these results could be compatible with a model in which distinct signals bias lineage choice and these signaling differences are not absolute or intrinsic to the specific TCR structure.