Towards a molecular understanding of the differential signals regulating αβ/γδ T lineage choice

While insights into the molecular processes that specify adoption of the αβ and γδ fates are beginning to emerge, the basis for control of specification remains highly controversial. This review highlights the current models attempting to explain T lineage commitment. Recent observations support the hypothesis that the T cell receptor (TCR) provides instructive cues through differences in TCR signaling intensity and/or longevity. Accordingly, we review evidence addressing the importance of differences in signal strength/longevity, how signals differing in intensity/longevity may be generated, and finally how such signals modulate the activity of downstream effectors to promote the opposing developmental fates.