Research Papers:
A structural model of the immune checkpoint CD160–HVEM complex derived from HDX-mass spectrometry and molecular modeling
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Abstract
Katarzyna Kuncewicz1, Marta Spodzieja1, Adam Sieradzan2, Agnieszka Karczyńska2, Katarzyna Dąbrowska3, Michał Dadlez3, Daniel E. Speiser4, Laurent Derre5 and Sylwia Rodziewicz-Motowidło1
1University of Gdansk, Faculty of Chemistry, Department of Biomedical Chemistry, Gdansk, Poland
2University of Gdansk, Faculty of Chemistry, Department of Theoretical Chemistry, Gdansk, Poland
3Polish Academy of Sciences, Institute of Biochemistry and Biophysics, Mass Spectrometry Laboratory, Warsaw, Poland
4Ludwig Cancer Research Center, Department of Oncology, Epalinges, Switzerland
5University Hospital of Lausanne (CHUV), Urology Department, Urology Research Unit, Lausanne, Switzerland
Correspondence to:
Sylwia Rodziewicz-Motowidło, email: s.rodziewicz-motowidlo@ug.edu.pl
Keywords: CD160; HVEM; immune checkpoints; hydrogen/deuterium exchange combined to mass spectrometry; molecular modeling
Received: May 13, 2018 Accepted: December 10, 2018 Published: January 11, 2019
ABSTRACT
CD160 is a T cell coinhibitory molecule that interacts with the herpes virus entry mediator (HVEM) on antigen-presenting cells to provide an inhibitory signal to T cells. To date, the structure of CD160 and its complex with HVEM are unknown. Here, we have identified the fragments of CD160 interacting with HVEM using ELISA tests, hydrogen/deuterium studies, affinity chromatography and mass spectrometry (MS). By combining hydrogen/deuterium exchange and mass spectrometry (HDX-MS) we obtained key information about the tertiary structure of CD160, predicting the 3D structure of the CD160–HVEM complex. Our results provide insights into the molecular architecture of this complex, serving as a useful basis for designing inhibitors for future immunotherapies.
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