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A structural model of the immune checkpoint CD160-HVEM complex derived from HDX-mass spectrometry and molecular modeling.

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.

SUBMITTER: Kuncewicz K

PROVIDER: S-EPMC6355189 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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A structural model of the immune checkpoint CD160-HVEM complex derived from HDX-mass spectrometry and molecular modeling.

Kuncewicz Katarzyna K Spodzieja Marta M Sieradzan Adam A Karczyńska Agnieszka A Dąbrowska Katarzyna K Dadlez Michał M Speiser Daniel E DE Derre Laurent L Rodziewicz-Motowidło Sylwia S

Oncotarget 20190111 4

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 i ...[more]

PMID: 30728903

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