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+1 Frameshifting as a Novel Mechanism to Generate a Cryptic Cytotoxic T Lymphocyte Epitope Derived from Human Interleukin 10
- 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.
- Subjects :
- DNA, Complementary
Molecular Sequence Data
Immunology
Clone (cell biology)
Biology
Transfection
Arthritis, Reactive
frameshift
Epitope
Frameshift mutation
Epitopes
Open Reading Frames
Animals
Humans
Immunology and Allergy
Cytotoxic T cell
Amino Acid Sequence
Frameshift Mutation
Gene
Peptide sequence
Genetics
epitope
COS cells
Base Sequence
Models, Genetic
autoimmunity
Models, Immunological
Brief Definitive Report
Frameshifting, Ribosomal
Clone Cells
Interleukin-10
Open reading frame
HLA-B Antigens
COS Cells
CTL
IL-10
Mutagenesis, Site-Directed
T-Lymphocytes, Cytotoxic
Subjects
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