Natural Killer (NK)1.1+ (NK1) T cells are a specialized subset of alpha/beta T cells that coexpress surface receptors that are normally associated with the NK cell lineage of the innate immune system. On recognition of the conserved, major histocompatibility complex class I- like CD1 molecule, these cells are able to release explosive bursts of interleukin 4 (IL-4), a cytokine that promotes the T helper type 2 (Th2) effector class of an immune response. A unique feature of their T cell receptor (TCR) repertoire is the expression of an invariant TCR alpha chain, V alpha 14-J alpha 281, and of a restricted but polyclonal set of V beta gene families, V beta 8, V beta 7, and V beta 2. Here, we show that transgenic expression of this TCR alpha chain during thymic development is sufficient information to bias the differentiation of mainstream thymocytes towards the NK1 developmental pathway. It markedly increases the frequency of cells with the NK1 pattern of T cell differentiation and also has drastic consequences for the selection of the V beta repertoire. Transgenic CD4 cells exhibited a 10- 100-fold increase in IL-4 production on mitogen stimulation in vitro and in vivo, and baseline levels of the Th2-controlled serum immunoglobulin isotypes, IgE and IgG1, were also selectively elevated in vivo.