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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4 February 2002
Brief Definitive Report|
February 04 2002
+1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10
Xavier Saulquin,
Xavier Saulquin
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
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Emmanuel Scotet,
Emmanuel Scotet
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
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Lydie Trautmann,
Lydie Trautmann
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
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Marie-Alix Peyrat,
Marie-Alix Peyrat
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
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Franck Halary,
Franck Halary
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
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Marc Bonneville,
Marc Bonneville
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
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Elisabeth Houssaint
Elisabeth Houssaint
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
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Xavier Saulquin
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
Emmanuel Scotet
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
Lydie Trautmann
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
Marie-Alix Peyrat
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
Franck Halary
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
Marc Bonneville
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
Elisabeth Houssaint
INSERM U463, Institut de Biologie, Nantes Cedex 01, France
Address correspondence to Elisabeth Houssaint, INSERM U463, Institut de Biologie, 9 Quai Moncousu, 44093 Nantes Cedex 01, France. Phone: 33-2-40-08-47-47; Fax: 33-2-40-35-66-97; E-mail: [email protected]
X. Saulquin and E. Scotet contributed equally to this work.
Received:
August 13 2001
Revision Received:
December 03 2001
Accepted:
December 11 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 195 (3): 353–358.
Article history
Received:
August 13 2001
Revision Received:
December 03 2001
Accepted:
December 11 2001
Citation
Xavier Saulquin, Emmanuel Scotet, Lydie Trautmann, Marie-Alix Peyrat, Franck Halary, Marc Bonneville, Elisabeth Houssaint; +1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10 . J Exp Med 4 February 2002; 195 (3): 353–358. doi: https://doi.org/10.1084/jem.20011399
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