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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

+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 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.[1]

References

  1. +1 Frameshifting as a novel mechanism to generate a cryptic cytotoxic T lymphocyte epitope derived from human interleukin 10. Saulquin, X., Scotet, E., Trautmann, L., Peyrat, M.A., Halary, F., Bonneville, M., Houssaint, E. J. Exp. Med. (2002) [Pubmed]
 
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