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TCR/pMHC Optimized Protein crystallization Screen

DOI: 10.1016/j.jim.2012.06.007 DOI Help

Authors: Anna Bulek (Cardiff University) , Florian Madura (Cardiff University) , Anna Fuller (Cardiff University) , Chris Holland (Cardiff University) , Andrea Schauenburg (Cardiff University) , Andrew K. Sewell , Pierre Rizkallah (Cardiff University) , David Cole (Cardiff University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Immunological Methods , VOL 382 , PAGES 203 - 210

State: Published (Approved)
Published: August 2012

Open Access Open Access

Abstract: The interaction between the clonotypic ?? 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.

Journal Keywords: Crystal structure; Peptide-major histocompatibility complex (pMHC); T cell receptor (TCR); Crystallization; X-ray diffraction; High throughput crystallization screen

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography