Notch activity influences the alphabeta versus gammadelta T cell lineage decision.
The choice between the alphabeta or gammadelta T cell fates is influenced by the production of functional, in-frame rearrangements of the TCR genes, but the mechanism that controls the lineage choice is not known. Here, we show that T cells that are heterozygous for a mutation of the Notch1 gene are more likely to develop as gammadelta T cells than as alphabeta T cells, implying that reduced Notch activity favors the gammadelta T cell fate over the alphabeta T cell fate. A constitutively activated form of Notch produces a reciprocal phenotype and induces thymocytes that have functional gammadeltaTCR gene rearrangements to adopt the alphabeta T cell fate. Our data indicate that Notch acts together with the newly formed T cell antigen receptor to direct the alphabeta versus gammadelta T cell lineage decision.
Washburn
T
T
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Schweighoffer
E
E
Gridley
T
T
Chang
D
D
Fowlkes
B J
BJ
Cado
D
D
Robey
E
E
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D018628:Gene Dosage; D015321:Gene Rearrangement; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006579:Heterozygote; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D019076:Transgenes / Q000276:immunology
D008565:Membrane Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins