Cytomegalovirus gp40/m152 Uses TMED10 as ER Anchor to Retain MHC Class I

Cell Rep. 2018 Jun 5;23(10):3068-3077. doi: 10.1016/j.celrep.2018.05.017.

Abstract

The murine cytomegalovirus immunoevasin m152/gp40 binds major histocompatibility complex (MHC) class I molecules and retains them in the early secretory pathway by a previously unknown mechanism, preventing antigen presentation to CD8+ T cells. We show that retention of class I and of gp40 itself depends on a lumenal linker sequence in gp40. With unbiased co-immunoprecipitation and mass spectrometry, we find that, through this linker, gp40 binds to TMED10/Tmp21/p24δ1, a member of the p24 family of endoplasmic reticulum (ER)/Golgi transmembrane proteins. We show that the C-terminal KKxxx Golgi-to-ER retrieval signal of TMED10 is required for gp40-mediated retention of class I. We thus identify a viral interaction partner of the p24 proteins and their exploitation for viral immune evasion.

Keywords: MHC class I; NKG2D ligand; gp40; immune evasion; m152; murine cytomegalovirus; p24 family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cell Line, Tumor
  • Endoplasmic Reticulum / metabolism*
  • Histocompatibility Antigens Class I / metabolism*
  • Immune Evasion
  • Mice
  • Models, Biological
  • Muromegalovirus / metabolism*
  • NIH 3T3 Cells
  • Protein Binding
  • Structure-Activity Relationship
  • Vesicular Transport Proteins / chemistry
  • Vesicular Transport Proteins / metabolism*
  • Viral Proteins / metabolism

Substances

  • Histocompatibility Antigens Class I
  • Tmed10 protein, mouse
  • Vesicular Transport Proteins
  • Viral Proteins