دورية أكاديمية
Structure-function relationships of chimeric antigen receptors in acute T cell responses to antigen.
| العنوان: | Structure-function relationships of chimeric antigen receptors in acute T cell responses to antigen. |
|---|---|
| المؤلفون: | Xu H; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Hamburger AE; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Mock JY; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Wang X; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Martin AD; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Tokatlian T; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Oh J; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Daris ME; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Negri KR; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Gabrelow GB; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Wu ML; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Nampe DP; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Asuelime GE; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., McElvain ME; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Sandberg ML; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States., Kamb A; A2 Biotherapeutics, 30301 Agoura Rd., Agoura Hills, CA, 91301, United States. Electronic address: akamb@a2biotherapeutics.com. |
| المصدر: | Molecular immunology [Mol Immunol] 2020 Oct; Vol. 126, pp. 56-64. Date of Electronic Publication: 2020 Aug 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Press Country of Publication: England NLM ID: 7905289 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9142 (Electronic) Linking ISSN: 01615890 NLM ISO Abbreviation: Mol Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, Elmsford, N. Y., Pergamon Press. |
| مواضيع طبية MeSH: | HLA-A Antigens/*immunology , Receptors, Chimeric Antigen/*metabolism , Signal Transduction/*immunology , T-Lymphocytes/*immunology, Binding Sites/immunology ; HLA-A Antigens/metabolism ; Humans ; Jurkat Cells ; Ligands ; MCF-7 Cells ; Protein Domains/immunology ; Protein Multimerization/immunology ; Receptors, Chimeric Antigen/immunology ; Structure-Activity Relationship ; T-Lymphocytes/metabolism |
| مستخلص: | Chimeric antigen receptors (CARs) and their parent signaling molecule, the T cell receptor (TCR), are fascinating proteins of increasing relevance to disease therapy. Here we use a collection of 1221 pMHC-directed CAR constructs representing 10 pMHC targets to study aspects of CAR structure-activity relationships (SAR), with particular focus on the extracellular and transmembrane structural components. These experiments that involve pMHC targets whose number/cell can be manipulated by peptide dosing in vitro enable systematic analysis of the SAR of CARs in carefully controlled experimental situations (Harris and Kranz, 2016). We find that CARs tolerate a wide range of structural variation, with the ligand-binding domains (LBDs) dominating the SAR of CAR antigen sensitivity. Notwithstanding the critical role of the LBD, CAR antigen-binding on the cell surface, measured by pMHC tetramer staining, is not an effective predictor of functional sensitivity. These results have important implications for the design and testing of CARs aimed toward the clinic. (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Antigen sensitivity; CAR; Cell therapy; SAR; TCR; pMHC |
| المشرفين على المادة: | 0 (HLA-A Antigens) 0 (Ligands) 0 (Receptors, Chimeric Antigen) |
| تواريخ الأحداث: | Date Created: 20200810 Date Completed: 20201109 Latest Revision: 20201109 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.molimm.2020.07.020 |
| PMID: | 32768859 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-9142 |
|---|---|
| DOI: | 10.1016/j.molimm.2020.07.020 |