A classical view of T cell lineages consists of two major clades of T cells expressing either the αβ or γδ T cell receptor (TCR). However, genome-wide assessments indicate molecular clusters segregating T cell subsets that are preprogrammed for effector function (innate) from those that mediate conventional adaptive response, regardless of the TCR types. Within this paradigm, γδ T cells remain the prototypic innate-like lymphocytes, many subsets of which are programmed during intrathymic development for committed peripheral tissue localization and effector responses. Emerging evidence for innate γδ T cell lineage choice dictated by developmental gene programs rather than the sensory TCR is discussed in this review.
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