A viral inhibitor of peptide transporters for antigen presentation (original) (raw)

Nature volume 375, pages 415–418 (1995)Cite this article

Abstract

CYTOTOXIC T lymphocytes lyse target cells after T-cell-receptor-mediated recognition of class I major histocompatibility complex molecules presenting peptides1. Antigenic peptides are generated in the cytoplasm by proteasomes2 and translocated into the lumen of the endoplasmic reticulum (ER) by peptide transporters (TAP)3–6. Herpes simplex virus (HSV) expresses a cytoplasmic protein, ICP47, which seems to interfere with such immune surveillance by mediating retention of 'empty' class I molecules in the ER7,8. By expressing ICP47 in HeLa cells under an inducible promoter9, we show that ICP47 efficiently inhibits peptide transport across the ER membrane such that nascent class I molecules fail to acquire antigenic peptides. This inhibition was overcome by transfecting murine TAP. Further, we demonstrate that ICP47 colocalizes and physically associates with TAP within the cell. Inhibition of peptide translocation by a viral protein indicates a previously undocumented potential mechanism for viral immune evasion.

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Authors and Affiliations

  1. Department of Immunology, The R.W. Johnson Pharmaceutical Research Institute at The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California, 92037, USA
    Klaus Früh, Kwangseog Ahn, Hakim Djaballah, Pascal Sempé, Per A. Peterson & Young Yang
  2. INSERM U25, Hospital Necker, 161 rue de Sevres, 75743, Paris, Cedex 15, France
    Peter M. van Endert
  3. Max-Planck-lnstitut für Biochemie, Abteilung für Strukturbiologie, 82152, Martinsried, Germany
    Robert Tampé

Authors

  1. Klaus Früh
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  2. Kwangseog Ahn
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  3. Hakim Djaballah
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  4. Pascal Sempé
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  5. Peter M. van Endert
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  6. Robert Tampé
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  7. Per A. Peterson
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  8. Young Yang
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Früh, K., Ahn, K., Djaballah, H. et al. A viral inhibitor of peptide transporters for antigen presentation.Nature 375, 415–418 (1995). https://doi.org/10.1038/375415a0

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