NOTCH ACTIVITY INFLUENCES THE ALPHA-BETA VERSUS GAMMA-DELTA T-CELL LINEAGE DECISION

The choice between the alpha beta or gamma delta T cell fates is influ enced by the production of functional, in-frame rearrangements of the TCR genes, but the mechanism that controls the lineage choice is not k nown. Here, we show that T cells that are heterozygous for a mutation of the Notch1 gene are more likely to develop as gamma delta T cells t han as alpha beta T cells, implying that reduced Notch activity favors the ya T cell fate over the alpha beta T cell fate. A constitutively activated form of Notch produces a reciprocal phenotype and induces th ymocytes that have functional gamma delta TCR gene rearrangements to a dopt the alpha beta T cell fate. Our data indicate that Notch acts tog ether with the newly formed T cell antigen receptor to direct the alph a beta versus gamma delta T cell lineage decision.