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Research Articles

Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity

Karoline Laske, Yuriy V. Shebzukhov, Ludger Grosse-Hovest, Dmitry V. Kuprash, Svetlana V. Khlgatian, Ekaterina P. Koroleva, Alexey Y. Sazykin, Dmitry N. Penkov, Pavel V. Belousov, Stefan Stevanović, Verona Vass, Steffen Walter, David Eisel, Barbara D. Schmid-Horch, Sergei A. Nedospasov, Hans-Georg Rammensee and Cécile Gouttefangeas
Karoline Laske
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Yuriy V. Shebzukhov
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Ludger Grosse-Hovest
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Dmitry V. Kuprash
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Svetlana V. Khlgatian
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Ekaterina P. Koroleva
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Alexey Y. Sazykin
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Dmitry N. Penkov
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Pavel V. Belousov
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Stefan Stevanović
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Verona Vass
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Steffen Walter
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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David Eisel
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Barbara D. Schmid-Horch
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Sergei A. Nedospasov
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Hans-Georg Rammensee
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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Cécile Gouttefangeas
1Department of Immunology, Institute for Cell Biology, Eberhard Karls University; 2Immatics Biotechnologies GmbH; 3Institute of Clinical and Experimental Transfusion Medicine, University Hospital, Tübingen, Germany; 4German Rheumatism Research Center, a Leibniz Institute, Berlin, Germany; 5Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University; and 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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DOI: 10.1158/2326-6066.CIR-13-0079 Published September 2013
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Abstract

A mutation in the hydin gene has been recently described as one possible mechanism leading to lethal congenital hydrocephalus in mice, and a similar defect is proposed to be involved in an autosomal recessive form of hydrocephalus in human. Here, we report for the first time on the cancer association and immunogenicity of two HYDIN variants in humans. One is a previously described sequence derived from the chromosome 1 gene copy, that is, KIAA1864. The second is encoded by a novel alternative transcript originating from the chromosome 16, which we identified by immunoscreening of a testis-derived cDNA expression library with sera of patients with colorectal cancer, and called MO-TES391. Both variants are targeted by immunoglobulin G antibodies in a significant subset of cancer patients but only rarely in healthy donors. Moreover, we identify HLA-A*0201–restricted sequences derived from MO-TES391 and KIAA1864, which are specifically recognized by human cytotoxic CD8+ T cells. Taken together, these results suggest frequent and coordinated adaptive immune responses against HYDIN variants in patients with cancer and propose HYDIN as a novel cancer-associated antigen. Cancer Immunol Res; 1(3); 190–200. ©2013 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • Received December 5, 2012.
  • Revision received April 22, 2013.
  • Accepted June 20, 2013.
  • ©2013 American Association for Cancer Research.
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Cancer Immunology Research: 1 (3)
September 2013
Volume 1, Issue 3
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Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity
Karoline Laske, Yuriy V. Shebzukhov, Ludger Grosse-Hovest, Dmitry V. Kuprash, Svetlana V. Khlgatian, Ekaterina P. Koroleva, Alexey Y. Sazykin, Dmitry N. Penkov, Pavel V. Belousov, Stefan Stevanović, Verona Vass, Steffen Walter, David Eisel, Barbara D. Schmid-Horch, Sergei A. Nedospasov, Hans-Georg Rammensee and Cécile Gouttefangeas
Cancer Immunol Res September 1 2013 (1) (3) 190-200; DOI: 10.1158/2326-6066.CIR-13-0079

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Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity
Karoline Laske, Yuriy V. Shebzukhov, Ludger Grosse-Hovest, Dmitry V. Kuprash, Svetlana V. Khlgatian, Ekaterina P. Koroleva, Alexey Y. Sazykin, Dmitry N. Penkov, Pavel V. Belousov, Stefan Stevanović, Verona Vass, Steffen Walter, David Eisel, Barbara D. Schmid-Horch, Sergei A. Nedospasov, Hans-Georg Rammensee and Cécile Gouttefangeas
Cancer Immunol Res September 1 2013 (1) (3) 190-200; DOI: 10.1158/2326-6066.CIR-13-0079
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