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+1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10

Recent data indicate that some cytotoxic T cells (CTLs) recognize so-called cryptic epitopes, encoded by nonprimary open reading frame (ORF) sequences or other nonclassical expression pathways. We describe here a novel mechanism leading to generation of a cryptic CTL epitope. We isolated from the sy...

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Autores principales: Saulquin, Xavier, Scotet, Emmanuel, Trautmann, Lydie, Peyrat, Marie-Alix, Halary, Franck, Bonneville, Marc, Houssaint, Elisabeth
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193594/
https://www.ncbi.nlm.nih.gov/pubmed/11828010
http://dx.doi.org/10.1084/jem.20011399
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author Saulquin, Xavier
Scotet, Emmanuel
Trautmann, Lydie
Peyrat, Marie-Alix
Halary, Franck
Bonneville, Marc
Houssaint, Elisabeth
author_facet Saulquin, Xavier
Scotet, Emmanuel
Trautmann, Lydie
Peyrat, Marie-Alix
Halary, Franck
Bonneville, Marc
Houssaint, Elisabeth
author_sort Saulquin, Xavier
collection PubMed
description Recent data indicate that some cytotoxic T cells (CTLs) recognize so-called cryptic epitopes, encoded by nonprimary open reading frame (ORF) sequences or other nonclassical expression pathways. We describe here a novel mechanism leading to generation of a cryptic CTL epitope. We isolated from the synovial fluid of a patient suffering from a Reiter's syndrome an autoreactive T cell clone that recognized cellular IL-10 in the HLA-B*2705 context. The minimal IL-10 sequence corresponding to nucleotides 379–408 was shown to activate this clone, upon cotransfection into COS cells with the DNA encoding HLA-B*2705, but the synthetic peptide deduced from this sequence did not stimulate the clone. Using a site-directed mutagenesis approach, we found that this clone recognized a transframe epitope generated by an internal +1 frameshifting in the IL-10 sequence and so derived partly from ORF1, partly from ORF2. We defined that +1 frameshifting was induced by a specific heptamer sequence. These observations illustrate the variety of mechanisms leading to generation of cryptic epitopes and suggest that frameshifting in normal cellular genes may be more common than expected.
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spelling pubmed-21935942008-04-14 +1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10 Saulquin, Xavier Scotet, Emmanuel Trautmann, Lydie Peyrat, Marie-Alix Halary, Franck Bonneville, Marc Houssaint, Elisabeth J Exp Med Brief Definitive Report Recent data indicate that some cytotoxic T cells (CTLs) recognize so-called cryptic epitopes, encoded by nonprimary open reading frame (ORF) sequences or other nonclassical expression pathways. We describe here a novel mechanism leading to generation of a cryptic CTL epitope. We isolated from the synovial fluid of a patient suffering from a Reiter's syndrome an autoreactive T cell clone that recognized cellular IL-10 in the HLA-B*2705 context. The minimal IL-10 sequence corresponding to nucleotides 379–408 was shown to activate this clone, upon cotransfection into COS cells with the DNA encoding HLA-B*2705, but the synthetic peptide deduced from this sequence did not stimulate the clone. Using a site-directed mutagenesis approach, we found that this clone recognized a transframe epitope generated by an internal +1 frameshifting in the IL-10 sequence and so derived partly from ORF1, partly from ORF2. We defined that +1 frameshifting was induced by a specific heptamer sequence. These observations illustrate the variety of mechanisms leading to generation of cryptic epitopes and suggest that frameshifting in normal cellular genes may be more common than expected. The Rockefeller University Press 2002-02-04 /pmc/articles/PMC2193594/ /pubmed/11828010 http://dx.doi.org/10.1084/jem.20011399 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Saulquin, Xavier
Scotet, Emmanuel
Trautmann, Lydie
Peyrat, Marie-Alix
Halary, Franck
Bonneville, Marc
Houssaint, Elisabeth
+1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10
title +1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10
title_full +1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10
title_fullStr +1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10
title_full_unstemmed +1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10
title_short +1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10
title_sort +1 frameshifting as a novel mechanism to generate a cryptic cytotoxic t lymphocyte epitope derived from human interleukin 10
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193594/
https://www.ncbi.nlm.nih.gov/pubmed/11828010
http://dx.doi.org/10.1084/jem.20011399
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