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

Authors :
Franck Halary
Elisabeth Houssaint
Marc Bonneville
Marie Alix Peyrat
Emmanuel Scotet
Lydie Trautmann
Xavier Saulquin
Source :
The Journal of Experimental Medicine
Publication Year :
2002
Publisher :
Rockefeller University Press, 2002.

Abstract

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.

Details

ISSN :
15409538 and 00221007
Volume :
195
Database :
OpenAIRE
Journal :
Journal of Experimental Medicine
Accession number :
edsair.doi.dedup.....f29bb99194832a088daac2d036ba4bb0
Full Text :
https://doi.org/10.1084/jem.20011399