دورية أكاديمية
Relevance of Nck-CD3 epsilon interaction for T cell activation in vivo.
العنوان: | Relevance of Nck-CD3 epsilon interaction for T cell activation in vivo. |
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المؤلفون: | Borroto A; Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain;, Arellano I, Blanco R, Fuentes M, Orfao A, Dopfer EP, Prouza M, Suchànek M, Schamel WW, Alarcón B |
المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Mar 01; Vol. 192 (5), pp. 2042-53. Date of Electronic Publication: 2014 Jan 27. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
مواضيع طبية MeSH: | Adaptor Proteins, Signal Transducing/*immunology , CD3 Complex/*immunology , Lymphocyte Activation/*physiology , Oncogene Proteins/*immunology , Receptors, Antigen, T-Cell/*immunology , T-Lymphocytes/*immunology, Adaptor Proteins, Signal Transducing/genetics ; Animals ; Antigens/genetics ; Antigens/immunology ; CD3 Complex/genetics ; Cell Proliferation ; Humans ; Jurkat Cells ; Mice ; Mice, Mutant Strains ; Oncogene Proteins/genetics ; Protein Structure, Tertiary ; Receptors, Antigen, T-Cell/genetics ; Signal Transduction/physiology ; T-Lymphocytes/cytology |
مستخلص: | On TCR ligation, the adaptor Nck is recruited through its src homology 3.1 domain to a proline-rich sequence (PRS) in CD3ε. We have studied the relevance of this interaction for T cell activation in vitro and in vivo by targeting the interaction sites in both partners. The first approach consisted of studying a knockin (KI) mouse line (KI-PRS) bearing a conservative mutation in the PRS that makes the TCR incompetent to recruit Nck. This deficiency prevents T cell activation by Ag in vitro and inhibited very early TCR signaling events including the tyrosine phosphorylation of CD3ζ. Most important, KI-PRS mice are partly protected against the development of neurological symptoms in an experimental autoimmune encephalitis model, and show a deficient antitumoral response after vaccination. The second approach consisted of using a high-affinity peptide that specifically binds the src homology 3.1 domain and prevents the interaction of Nck with CD3ε. This peptide inhibits T cell proliferation in vitro and in vivo. These data suggest that Nck recruitment to the TCR is fundamental to mount an efficient T cell response in vivo, and that the Nck-CD3ε interaction may represent a target for pharmacological modulation of the immune response. |
المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) 0 (Antigens) 0 (CD3 Complex) 0 (CD3E protein, human) 0 (Cd3e protein, mouse) 0 (Nck protein) 0 (Oncogene Proteins) 0 (Receptors, Antigen, T-Cell) |
تواريخ الأحداث: | Date Created: 20140129 Date Completed: 20140418 Latest Revision: 20171116 |
رمز التحديث: | 20240628 |
DOI: | 10.4049/jimmunol.1203414 |
PMID: | 24470497 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1550-6606 |
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DOI: | 10.4049/jimmunol.1203414 |