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TCR/pMHC optimized protein crystallization screen

Bulek, Anna Marta, Madura, Florian, Fuller, Anna, Holland, Christopher J., Schauenburg, Andrea J. A., Sewell, Andrew K., Rizkallah, Pierre and Cole, David 2012. TCR/pMHC optimized protein crystallization screen. Journal of Immunological Methods 382 (1-2) , pp. 203-210. 10.1016/j.jim.2012.06.007

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Abstract

The interaction between the clonotypic αβ T cell receptor (TCR), expressed on the T cell surface, and peptide-major histocompatibility complex (pMHC) molecules, expressed on the target cell surface, governs T cell mediated autoimmunity and immunity against pathogens and cancer. Structural investigations of this interaction have been limited because of the challenges inherent in the production of good quality TCR/pMHC protein crystals. Here, we report the development of an ‘intelligently designed’ crystallization screen that reproducibly generates high quality TCR/pMHC complex crystals suitable for X-ray crystallographic studies, thereby reducing protein consumption. Over the last 2 years, we have implemented this screen to produce 32 T cell related protein structures at high resolution, substantially contributing to the current immune protein database. Protein crystallography, used to study this interaction, has already extended our understanding of the molecular rules that govern T cell immunity. Subsequently, these data may help to guide the intelligent design of T cell based therapies that target human diseases, underlining the importance of developing optimized approaches for crystallizing novel TCR/pMHC complexes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: crystal structure, peptide-major histocompatibility complex (pMHC), T cell receptor (TCR), crystallization, x-ray diffraction, high throughput crystallization screen
Publisher: Elsevier
ISSN: 0022-1759
Last Modified: 13 Jan 2018 20:20
URI: http://orca.cf.ac.uk/id/eprint/41063

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