The murine cytomegalovirus immunoevasin gp40/m152 inhibits activation of NK cell receptor NKG2D by intracellular retention and cell surface masking of RAE-1 gamma ligand

  • NKG2D is a crucial Natural Killer (NK) cell activating receptor, and the murine cytomegalovirus (MCMV) employs multiple immunoevasins in order to avoid NKG2D-mediated activation. One of the MCMV immunoevasins, gp40 (m152), downregulates the cell surface NKG2D ligand, RAE-1 gamma, thus limiting NK cell activation. My study establishes the molecular mechanism by which gp40 retains RAE-1 gamma in the secretory pathway. Using flow cytometry and pulse chase analysis, I demonstrate that gp40 retains RAE-1 gamma in the early secretory pathway, and that this effect depends on the binding of gp40 to a host protein, TMED10, a member of the p24 protein family. I also show that the TMED10-based retention mechanism can be saturated, and that gp40 has a backup mechanism as it masks RAE-1 gamma on the cell surface, blocking the interaction with the NKG2D receptor and thus NK cell activation.

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Meta data
Publishing Institution:IRC-Library, Information Resource Center der Jacobs University Bremen
Granting Institution:Jacobs Univ.
Author:Natalia Lis
Referee:Sebastian Springer, Susanne Illenberger, Wolfram Brune
Advisor:Sebastian Springer
Persistent Identifier (URN):urn:nbn:de:gbv:579-opus-1009369
Document Type:PhD Thesis
Language:English
Date of Successful Oral Defense:2020/04/09
Date of First Publication:2020/11/25
Academic Department:Life Sciences & Chemistry
PhD Degree:Cell Biology
Focus Area:Health
Call No:2020/12

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