Stable, soluble T-cell receptor molecules for crystallization and therapeutics

Stable, soluble T-cell receptor molecules for crystallization and therapeutics
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DOI:
10.1093/protein/gzg087
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发表时间:
2003-09-01
期刊:
PROTEIN ENGINEERING
影响因子:
--
通讯作者:
Jakobsen, BK
Jakobsen, BK
中科院分区:
其他
文献类型:
--
作者:
Boulter, JM;Glick, M;Jakobsen, BK

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抗体和 T 细胞受体 (TCR) 是适应性免疫系统的主要识别分子。抗体已被广泛表征并正在开发用于大量治疗应用。这是可能的,因为能够制造稳定的、可溶的、保留 B 细胞抗原特异性的单克隆抗体。与抗体不同,TCR 不以可溶形式表达,而是通过不溶性跨膜结构域锚定在 T 细胞表面。由于缺乏合适的方法将 TCR 生产为可溶且稳定的蛋白质,TCR 的表征和开发受到了阻碍。在此,我们报告了适用于结晶研究并可能用于体内治疗用途的可溶性人类 TCR 的工程。
Antibody and T-cell receptors (TCRs) are the primary recognition molecules of the adaptive immune system. Antibodies have been extensively characterized and are being developed for a large number of therapeutic applications. This has been possible because of the ability to manufacture stable, soluble, monoclonal antibodies which retain the antigen specificity of B cells. Unlike antibodies, TCRs are not expressed in a soluble form, but are anchored to the T-cell surface by an insoluble trans-membrane domain. Characterization and development of TCRs has been hampered by the lack of suitable methods for producing them as soluble and stable proteins. Here we report the engineering of soluble human TCRs suitable for crystallization studies and potentially for in vivo therapeutic use.