TCR signal strength influences alphabeta/gammadelta lineage fate.
Signals transduced by T cell antigen receptors (TCRs) have been shown to be critical for alphabeta and gammadelta T cell development, but their role in lineage determination remains poorly defined. Two models have been forwarded for alphabeta/gammadelta lineage choice: the instructive model and the stochastic model. Recent data, however, are inconsistent with either model. In this study, we devised an experimental system in which lineage fate was controlled exclusively by the gammadeltaTCR. We then analyzed the impact of TCR signal strength on alphabeta/gammadelta lineage development by altering the surface expression or signaling potential of the gammadeltaTCR complex. We found that increasing the gammadeltaTCR signal strength favored gammadelta lineage development, whereas weakening the gammadeltaTCR signal favored alphabeta lineage development. These results support a model in which the strength of the TCR signal is a critical determinant in the lineage fate decision.
Hayes
Sandra M
SM
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development/NIH, Bethesda, MD 20892, USA.
Li
Liqi
L
Love
Paul E
PE
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*
D018076:DNA, Complementary; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins