The ER-luminal domain of the HCMV glypcoprotein US6 inhibits peptide translocation by TAP

Kwangseog Ahn, Albrecht Gruhler, Begona Galocha, Thomas R. Jones, Emmanuel J H J Wiertz, Hidde L. Ploegh, Per A. Peterson, Young Yang, Klaus Frueh

Research output: Contribution to journalArticle

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Abstract

Human cytomegalovirus (HCMV) inhibits MHC class I antigen presentation by a sequential multistep process involving a family of unique short (US) region-encoded glycoproteins. US3 retains class I molecules, whereas US2 and US11 mediate the cytosolic degradation of heavy chains by the proteosomes. In US6-transfected cells, however, intracellular transport of class I molecules is impaired because of defective peptide translocation by transporters associated with antigen processing (TAP). Peptide transport is restored in HCMV mutants lacking US6. In contrast to the cytosolic herpes simplex virus protein ICP47, US6 interacts with TAP inside the endoplasmic reticulum lumen, as shown by US6 derivatives lacking the transmembrane and cytoplasmic domains and by the observation that US6 does not prevent peptides from binding to TAP. Thus, HCMV targets TAP for immune escape by a molecular mechanism different from that of herpes simplex virus.

Original languageEnglish (US)
Pages (from-to)613-621
Number of pages9
JournalImmunity
Volume6
Issue number5
DOIs
StatePublished - May 1997
Externally publishedYes

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trypsinogen activation peptide
Cytomegalovirus
Histocompatibility Antigens Class I
Peptides
Antigen Presentation
Simplexvirus
Endoplasmic Reticulum
Glycoproteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Ahn, K., Gruhler, A., Galocha, B., Jones, T. R., Wiertz, E. J. H. J., Ploegh, H. L., ... Frueh, K. (1997). The ER-luminal domain of the HCMV glypcoprotein US6 inhibits peptide translocation by TAP. Immunity, 6(5), 613-621. https://doi.org/10.1016/S1074-7613(00)80349-0

The ER-luminal domain of the HCMV glypcoprotein US6 inhibits peptide translocation by TAP. / Ahn, Kwangseog; Gruhler, Albrecht; Galocha, Begona; Jones, Thomas R.; Wiertz, Emmanuel J H J; Ploegh, Hidde L.; Peterson, Per A.; Yang, Young; Frueh, Klaus.

In: Immunity, Vol. 6, No. 5, 05.1997, p. 613-621.

Research output: Contribution to journalArticle

Ahn, K, Gruhler, A, Galocha, B, Jones, TR, Wiertz, EJHJ, Ploegh, HL, Peterson, PA, Yang, Y & Frueh, K 1997, 'The ER-luminal domain of the HCMV glypcoprotein US6 inhibits peptide translocation by TAP', Immunity, vol. 6, no. 5, pp. 613-621. https://doi.org/10.1016/S1074-7613(00)80349-0
Ahn K, Gruhler A, Galocha B, Jones TR, Wiertz EJHJ, Ploegh HL et al. The ER-luminal domain of the HCMV glypcoprotein US6 inhibits peptide translocation by TAP. Immunity. 1997 May;6(5):613-621. https://doi.org/10.1016/S1074-7613(00)80349-0
Ahn, Kwangseog ; Gruhler, Albrecht ; Galocha, Begona ; Jones, Thomas R. ; Wiertz, Emmanuel J H J ; Ploegh, Hidde L. ; Peterson, Per A. ; Yang, Young ; Frueh, Klaus. / The ER-luminal domain of the HCMV glypcoprotein US6 inhibits peptide translocation by TAP. In: Immunity. 1997 ; Vol. 6, No. 5. pp. 613-621.
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