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Nattermann J, Nischalke HD, Hofmeister V, et al. The HLA-A2 restricted T cell epitope HCV core 35-44 stabilizes HLA-E expression and inhibits cytolysis mediated by natural killer cells. Am J Pathol. 2005;166(2):443-53doi: 10.1016/S0002-9440(10)62267-5.
Nattermann, J., Nischalke, H. D., Hofmeister, V., Ahlenstiel, G., Zimmermann, H., Leifeld, L., Weiss, E. H., Sauerbruch, T., & Spengler, U. (2005). The HLA-A2 restricted T cell epitope HCV core 35-44 stabilizes HLA-E expression and inhibits cytolysis mediated by natural killer cells. The American journal of pathology, 166(2), 443-53. https://doi.org/10.1016/S0002-9440(10)62267-5
Nattermann, Jacob, et al. "The HLA-A2 restricted T cell epitope HCV core 35-44 stabilizes HLA-E expression and inhibits cytolysis mediated by natural killer cells." The American journal of pathology vol. 166,2 (2005): 443-53. doi: https://doi.org/10.1016/S0002-9440(10)62267-5
Nattermann J, Nischalke HD, Hofmeister V, Ahlenstiel G, Zimmermann H, Leifeld L, Weiss EH, Sauerbruch T, Spengler U. The HLA-A2 restricted T cell epitope HCV core 35-44 stabilizes HLA-E expression and inhibits cytolysis mediated by natural killer cells. Am J Pathol. 2005 Feb;166(2):443-53. doi: 10.1016/S0002-9440(10)62267-5. PMID: 15681828; PMCID: PMC1602324.
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Am J Pathol. 2005 Feb;166(2):443-53. doi: 10.1016/S0002-9440(10)62267-5.

The HLA-A2 restricted T cell epitope HCV core 35-44 stabilizes HLA-E expression and inhibits cytolysis mediated by natural killer cells.

The American journal of pathology

Jacob Nattermann, Hans Dieter Nischalke, Valeska Hofmeister, Golo Ahlenstiel, Henning Zimmermann, Ludger Leifeld, Elisabeth H Weiss, Tilman Sauerbruch, Ulrich Spengler

Affiliations

  1. Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. [email protected]

PMID: 15681828 PMCID: PMC1602324 DOI: 10.1016/S0002-9440(10)62267-5

Abstract

Impaired activity of natural killer cells has been proposed as a mechanism contributing to viral persistence in hepatitis C virus (HCV) infection. Natural cytotoxicity is regulated by interactions of HLA-E with inhibitory CD94/NKG2A receptors on natural killer (NK) cells. Here, we studied whether HCV core encodes peptides that bind to HLA-E and inhibit natural cytotoxicity. We analyzed 30 HCV core-derived peptides. Peptide-induced stabilization of HLA-E expression was measured flow cytometrically after incubating HLA-E-transfected cells with peptides. NK cell function was studied with a (51)chromium-release-assay. Intrahepatic HLA-E expression was analyzed by an indirect immunoperoxidase technique and flow cytometry of isolated cells using a HLA-E-specific antibody. We identified peptide aa35-44, a well-characterized HLA-A2 restricted T cell epitope, as a peptide stabilizing HLA-E expression and thereby inhibiting NK cell-mediated lysis. Blocking experiments confirmed that this inhibitory effect of peptide aa35-44 on natural cytotoxicity was mediated via interactions between CD94/NKG2A receptors and enhanced HLA-E expression. In line with these in vitro data we found enhanced intrahepatic HLA-E expression on antigen-presenting cells in HCV-infected patients. Our data indicate the existence of T cell epitopes that can be recognized by HLA-A2 and HLA-E. This dual recognition may contribute to viral persistence in hepatitis C.

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