A viral inhibitor of peptide transporters for antigen presentation (original) (raw)
- Letter
- Published: 01 June 1995
- Kwangseog Ahn1,
- Hakim Djaballah1,
- Pascal Sempé1,
- Peter M. van Endert2,
- Robert Tampé3,
- Per A. Peterson1 &
- …
- Young Yang1
Nature volume 375, pages 415–418 (1995)Cite this article
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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
- 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 - INSERM U25, Hospital Necker, 161 rue de Sevres, 75743, Paris, Cedex 15, France
Peter M. van Endert - Max-Planck-lnstitut für Biochemie, Abteilung für Strukturbiologie, 82152, Martinsried, Germany
Robert Tampé
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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
- Received: 01 March 1995
- Accepted: 18 April 1995
- Issue Date: 01 June 1995
- DOI: https://doi.org/10.1038/375415a0