Signaling of a varicelloviral factor across the endoplasmic reticulum membrane induces destruction of the peptide-loading complex and immune evasion

Sandra Loch, Florian Klauschies, Christian Schölz, Marieke Verweij, Emmanuel J H J Wiertz, Joachim Koch, Robert Tampé

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cytotoxic T lymphocytes eliminate infected cells upon surface display of antigenic peptides on major histocompatibility complex I molecules. To promote immune evasion, UL49.5 of several varicelloviruses interferes with the pathway of major histocompatibility complex I antigen processing. However, the inhibition mechanism has not been elucidated yet. Within the macromolecular peptide-loading complex we identified the transporter associated with antigen processing (TAP1 and TAP2) as the prime target of UL49.5. Moreover, we determined the active oligomeric state and crucial elements of the viral factor. Remarkably, the last two residues of the cytosolic tail of UL49.5 are essential for endoplasmic reticulum (ER)-associated proteasomal degradation of TAP. However, this process strictly requires additional signaling of an upstream regulatory element in the ER lumenal domain of UL49.5. Within this new immune evasion mechanism, we show for the first time that additive elements of a small viral factor and their signaling across the ER membrane are essential for targeted degradation of a multi-subunit membrane complex.

Original languageEnglish (US)
Pages (from-to)13428-13430
Number of pages3
JournalJournal of Biological Chemistry
Volume283
Issue number19
DOIs
StatePublished - May 9 2008
Externally publishedYes

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Immune Evasion
Antigen Presentation
Antigen-Antibody Complex
Major Histocompatibility Complex
Endoplasmic Reticulum
Varicellovirus
Endoplasmic Reticulum-Associated Degradation
Membranes
Degradation
Peptides
T-cells
Cytotoxic T-Lymphocytes
Processing
Display devices
Antigens
Molecules
I-antigen

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Signaling of a varicelloviral factor across the endoplasmic reticulum membrane induces destruction of the peptide-loading complex and immune evasion. / Loch, Sandra; Klauschies, Florian; Schölz, Christian; Verweij, Marieke; Wiertz, Emmanuel J H J; Koch, Joachim; Tampé, Robert.

In: Journal of Biological Chemistry, Vol. 283, No. 19, 09.05.2008, p. 13428-13430.

Research output: Contribution to journalArticle

Loch, Sandra ; Klauschies, Florian ; Schölz, Christian ; Verweij, Marieke ; Wiertz, Emmanuel J H J ; Koch, Joachim ; Tampé, Robert. / Signaling of a varicelloviral factor across the endoplasmic reticulum membrane induces destruction of the peptide-loading complex and immune evasion. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 19. pp. 13428-13430.
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