Differential SLP-76 Expression and TCR-Mediated Signaling in Effector and Memory CD4 T Cells
| Autor: | Donna L. Farber, S. Farzana Hussain, Charles F. Anderson |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
CD4-Positive T-Lymphocytes
MAP Kinase Signaling System Blotting Western Immunology Receptors Antigen T-Cell Linker for Activation of T cells Biology Lymphocyte Activation Mice T-Lymphocyte Subsets Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor Phosphorylation Cells Cultured Adaptor Proteins Signal Transducing GRB2 Adaptor Protein Mice Inbred BALB C Effector ZAP70 T-cell receptor Models Immunological Proteins Phosphoproteins Precipitin Tests Cell biology Mitogen-activated protein kinase biology.protein Immunologic Memory |
| Zdroj: | The Journal of Immunology. 168:1557-1565 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.168.4.1557 |
| Popis: | We present in this study novel findings on TCR-mediated signaling in naive, effector, and memory CD4 T cells that identify critical biochemical markers to distinguish these subsets. We demonstrate that relative to naive CD4 T cells, memory CD4 T cells exhibit a profound decrease in expression of the linker/adapter molecule SLP-76, while effector T cells express normal to elevated levels of SLP-76. The reduced level of SLP-76 is memory CD4 T cells is coincident with reduced phosphorylation overall, yet the residual SLP-76 couples to a subset of TCR-associated linker molecules, leading to downstream mitogen-activated protein (MAP) kinase activation. By contrast, effector CD4 T cells strongly phosphorylate SLP-76, linker for activation of T cells, and additional Grb2-coupled proteins, exhibit increased associations of SLP-76 to phosphorylated linkers, and hyperphosphorylate downstream Erk1/2 MAP kinases. Our results suggest distinct coupling of signaling intermediates to the TCR in naive, effector, and memory CD4 T cells. Whereas effector CD4 T cells amplify existing TCR signaling events accounting for rapid effector responses, memory T cells engage fewer signaling intermediates to efficiently link TCR triggering directly to downstream MAP kinase activation. |
| Databáze: | OpenAIRE |
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