Obligatory Role for Cooperative Signaling by Pre-TCR and Notch during Thymocyte Differentiation
The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR-beta gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch receptor-ligand interactions are necessary dur...
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| Published in | The Journal of immunology (1950) Vol. 172; no. 9; pp. 5230 - 5239 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Am Assoc Immnol
01.05.2004
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| Subjects | |
| Online Access | Get full text |
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| Abstract | The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR-beta gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch receptor-ligand interactions are necessary during beta selection. Here, we show that pre-TCR signaling concurrent with Notch receptor and Delta-like-1 ligand interactions are required for the survival, proliferation, and differentiation of mouse CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage. Furthermore, we address the minimal signaling requirements underlying beta selection and show a hierarchical positioning of key proximal signaling molecules. Collectively, our results demonstrate an essential role for Notch receptor-ligand interactions in enabling the autonomous signaling capacity of the pre-TCR complex. |
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| AbstractList | The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR-beta gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch receptor-ligand interactions are necessary during beta selection. Here, we show that pre-TCR signaling concurrent with Notch receptor and Delta-like-1 ligand interactions are required for the survival, proliferation, and differentiation of mouse CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage. Furthermore, we address the minimal signaling requirements underlying beta selection and show a hierarchical positioning of key proximal signaling molecules. Collectively, our results demonstrate an essential role for Notch receptor-ligand interactions in enabling the autonomous signaling capacity of the pre-TCR complex. The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR- beta gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch receptor-ligand interactions are necessary during beta selection. Here, we show that pre-TCR signaling concurrent with Notch receptor and Delta-like-1 ligand interactions are required for the survival, proliferation, and differentiation of mouse CD4 super(-)CD8 super(-) thymocytes to the CD4 super(+)CD8 super(+) stage. Furthermore, we address the minimal signaling requirements underlying beta selection and show a hierarchical positioning of key proximal signaling molecules. Collectively, our results demonstrate an essential role for Notch receptor-ligand interactions in enabling the autonomous signaling capacity of the pre-TCR complex. Abstract The first checkpoint during T cell development, known as β selection, requires the successful rearrangement of the TCR-β gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch receptor-ligand interactions are necessary during β selection. Here, we show that pre-TCR signaling concurrent with Notch receptor and Delta-like-1 ligand interactions are required for the survival, proliferation, and differentiation of mouse CD4−CD8− thymocytes to the CD4+CD8+ stage. Furthermore, we address the minimal signaling requirements underlying β selection and show a hierarchical positioning of key proximal signaling molecules. Collectively, our results demonstrate an essential role for Notch receptor-ligand interactions in enabling the autonomous signaling capacity of the pre-TCR complex. |
| Author | Schmitt, Thomas M Cuburu, Nicolas Aublin, Anne Ciofani, Amelia Michie, Alison M Zuniga-Pflucker, Juan Carlos Ciofani, Maria Maryanski, Janet L |
| Author_xml | – sequence: 1 fullname: Ciofani, Maria – sequence: 2 fullname: Schmitt, Thomas M – sequence: 3 fullname: Ciofani, Amelia – sequence: 4 fullname: Michie, Alison M – sequence: 5 fullname: Cuburu, Nicolas – sequence: 6 fullname: Aublin, Anne – sequence: 7 fullname: Maryanski, Janet L – sequence: 8 fullname: Zuniga-Pflucker, Juan Carlos |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/15100261$$D View this record in MEDLINE/PubMed |
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| Snippet | The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR-beta gene locus. Notch signaling has... Abstract The first checkpoint during T cell development, known as β selection, requires the successful rearrangement of the TCR-β gene locus. Notch signaling... The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR- beta gene locus. Notch signaling has... |
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| SubjectTerms | Animals Antibodies, Monoclonal - administration & dosage CD3 Complex - immunology Cell Differentiation - genetics Cell Differentiation - immunology Cell Division - genetics Cell Division - immunology Cell Line Coculture Techniques DNA-Binding Proteins - deficiency DNA-Binding Proteins - genetics Fetus Gene Rearrangement, beta-Chain T-Cell Antigen Receptor Genes, T-Cell Receptor beta - physiology Intracellular Signaling Peptides and Proteins Ligands Membrane Glycoproteins - biosynthesis Membrane Glycoproteins - genetics Membrane Glycoproteins - physiology Membrane Proteins - metabolism Membrane Proteins - physiology Mice Mice, Knockout Protein Precursors - biosynthesis Protein Precursors - genetics Protein Precursors - physiology Receptors, Antigen, T-Cell, alpha-beta Receptors, Notch Signal Transduction - genetics Signal Transduction - immunology Stromal Cells - immunology Stromal Cells - metabolism T-Lymphocyte Subsets - cytology T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Thymus Gland - cytology Thymus Gland - immunology Thymus Gland - metabolism |
| Title | Obligatory Role for Cooperative Signaling by Pre-TCR and Notch during Thymocyte Differentiation |
| URI | http://www.jimmunol.org/cgi/content/abstract/172/9/5230 https://www.ncbi.nlm.nih.gov/pubmed/15100261 https://search.proquest.com/docview/17966710 https://search.proquest.com/docview/71852297 |
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