Differential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy.
Ag recognition triggered at the interface between a T cell and an APC is conditioned by cell-cell adhesion and cytoskeletal remodeling. The role played in these phenomena by Lck and Itk, two protein tyrosine kinases essential for T cell signaling, was examined. Early T cell responses (membrane ruffl...
| المؤلفون الرئيسيون: | , , , , , , |
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| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
2001
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| _version_ | 1826270607158804480 |
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| author | Donnadieu, E Lang, V Bismuth, G Ellmeier, W Acuto, O Michel, F Trautmann, A |
| author_facet | Donnadieu, E Lang, V Bismuth, G Ellmeier, W Acuto, O Michel, F Trautmann, A |
| author_sort | Donnadieu, E |
| collection | OXFORD |
| description | Ag recognition triggered at the interface between a T cell and an APC is conditioned by cell-cell adhesion and cytoskeletal remodeling. The role played in these phenomena by Lck and Itk, two protein tyrosine kinases essential for T cell signaling, was examined. Early T cell responses (membrane ruffling, Ca(2+) response, APC-T cell adhesion) were monitored in T cells overexpressing kinase-defective (KD) Lck and Itk mutants by combining fluorescence imaging and electron microscopy. Neither Lck nor Itk appears to be involved in the Ag-independent formation of a small and labile contact interface between T cells and APCS: By contrast, the Ag-induced Ca(2+) response in a cell population is similarly blunted in both KD transfectants. However, the underlying mechanisms are strikingly different for the two kinases. The major effect of Lck-KD is to reduce the probability of giving rise to quasi-normal Ca(2+) responses, whereas overexpression of Itk-KD results in a tuning down of all single-cell Ca(2+) responses. In addition, Lck, but not Itk, is required for the formation of a stable T/APC conjugate and for T cell polarization after Ag stimulation. Overall, our results lead to a clear distinction between Lck and ITK: Lck plays an ignition role, controlling all the downstream events tested here, whereas Itk amplifies the Ca(2+) response, but is dispensable for APC-induced adhesive and morphological responses. |
| first_indexed | 2024-03-06T21:43:30Z |
| format | Journal article |
| id | oxford-uuid:48c0c7cc-f973-4b03-82b5-dfc2ddc6fae9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:43:30Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:48c0c7cc-f973-4b03-82b5-dfc2ddc6fae92022-03-26T15:27:33ZDifferential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:48c0c7cc-f973-4b03-82b5-dfc2ddc6fae9EnglishSymplectic Elements at Oxford2001Donnadieu, ELang, VBismuth, GEllmeier, WAcuto, OMichel, FTrautmann, AAg recognition triggered at the interface between a T cell and an APC is conditioned by cell-cell adhesion and cytoskeletal remodeling. The role played in these phenomena by Lck and Itk, two protein tyrosine kinases essential for T cell signaling, was examined. Early T cell responses (membrane ruffling, Ca(2+) response, APC-T cell adhesion) were monitored in T cells overexpressing kinase-defective (KD) Lck and Itk mutants by combining fluorescence imaging and electron microscopy. Neither Lck nor Itk appears to be involved in the Ag-independent formation of a small and labile contact interface between T cells and APCS: By contrast, the Ag-induced Ca(2+) response in a cell population is similarly blunted in both KD transfectants. However, the underlying mechanisms are strikingly different for the two kinases. The major effect of Lck-KD is to reduce the probability of giving rise to quasi-normal Ca(2+) responses, whereas overexpression of Itk-KD results in a tuning down of all single-cell Ca(2+) responses. In addition, Lck, but not Itk, is required for the formation of a stable T/APC conjugate and for T cell polarization after Ag stimulation. Overall, our results lead to a clear distinction between Lck and ITK: Lck plays an ignition role, controlling all the downstream events tested here, whereas Itk amplifies the Ca(2+) response, but is dispensable for APC-induced adhesive and morphological responses. |
| spellingShingle | Donnadieu, E Lang, V Bismuth, G Ellmeier, W Acuto, O Michel, F Trautmann, A Differential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy. |
| title | Differential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy. |
| title_full | Differential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy. |
| title_fullStr | Differential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy. |
| title_full_unstemmed | Differential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy. |
| title_short | Differential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy. |
| title_sort | differential roles of lck and itk in t cell response to antigen recognition revealed by calcium imaging and electron microscopy |
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