T-cell activation through the antigen receptor. Part 2: Role of signaling cascades in T-cell differentiation, anergy, immune senescence, and development of immunotherapy
| Autor: | Andre E. Nel, Ndaisha Slaughter |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Transcriptional Activation
Immunoconjugates T-Lymphocytes T cell Immunology Receptors Antigen T-Cell Antigen-Presenting Cells chemical and pharmacologic phenomena Biology Lymphocyte Activation Immunotherapy Adoptive Models Biological Abatacept Antigens CD Immunoreceptor tyrosine-based activation motif medicine Humans Immunology and Allergy CTLA-4 Antigen Phosphorylation Promoter Regions Genetic Protein kinase A Protein kinase C Clonal Anergy T-cell receptor Cell Differentiation hemic and immune systems Protein-Tyrosine Kinases Antigens Differentiation medicine.anatomical_structure STAT protein Cancer research Cytokines Calcium Signal transduction Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Allergy and Clinical Immunology. 109:901-915 |
| ISSN: | 0091-6749 |
| DOI: | 10.1067/mai.2002.124965 |
| Popis: | Part 2 of this review on cellular activation by the T-cell antigen receptor (TCR) will highlight how TCR signaling pathways are adapted to achieve specific biologic outcomes, including different states of T-cell differentiation and the induction of T-cell tolerance. We will also explore how treatment with altered peptide ligands affects TCR signaling to change T-cell differentiation or to induce an anergy state. These changes are accomplished through alteration of protein tyrosine kinase activity, the stoichiometry of phosphorylation of immunoreceptor tyrosine-based activation motifs, intracellular free ionized calcium flux, mitogen-activated protein kinase activity, and transcriptional activation of key cytokine promoters. The CTLA-4 plays an important role in the induction and maintenance of anergy. The second theme will highlight how altered TCR signal transduction, including changes in the compartmentalization of signaling components at the TCR synapse, contributes to decreased T-cell activation during immune senescence. Finally, we will illustrate how the molecular details of TCR activation can be used to modify the function of the immune system. This includes a description of the mechanism of action of altered peptide ligands, CTLA-4Ig, and pharmacologic inhibitors of mitogen-activated protein kinases, nuclear factor kappaB, and protein kinase C cascades. |
| Databáze: | OpenAIRE |
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