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An alternative open reading frame of the human macrophage colony-stimulating factor gene is independently translated and codes for an antigenic peptide of 14 amino acids recognized by tumor-infiltrating CD8 T lymphocytes.

Probst-Kepper, Michael;Stroobant, Vincent;Kridel, Robert;Gaugler, Béatrice;Van den Eynde, Benoit;et.al.
(2001) The Journal of Experimental Medicine — Vol. 193, n° 10, p. 1189-1198 (2001)

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Authors
  • Probst-Kepper, MichaelUCLouvain
    Author
  • Stroobant, VincentUCLouvain
    Author
  • Kridel, RobertUCLouvain
    Author
  • Gaugler, BéatriceUCLouvain
    Author
  • Landry, ClaireUCLouvain
    Author
  • Brasseur, FrancisUCLouvain
    Author
  • Cosyns, Jean-PierreUCLouvain
    Author
  • Weynand, BirgitUCLouvain
    Author
  • Boon, ThierryUCLouvain
    Author
  • Van den Eynde, Benoitorcid-logoUCLouvain
    Author
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Abstract
We show that cytotoxic T lymphocytes (CTLs) infiltrating a kidney tumor recognize a peptide encoded by an alternative open reading frame (ORF) of the macrophage colony-stimulating factor (M-CSF) gene. Remarkably, this alternative ORF, which is translated in many tumors concurrently with the major ORF, is also translated in some tissues that do not produce M-CSF, such as liver and kidney. Such a dissociation of the translation of two overlapping ORFs from the same gene is unexpected. The antigenic peptide encoded by the alternative ORF is presented by human histocompatibility leukocyte antigen (HLA)-B*3501 and has a length of 14 residues. Peptide elution indicated that tumor cells naturally present this 14 mer, which is the longest peptide known to be recognized by CTLs. Binding studies of peptide analogues suggest that it binds by its two extremities and bulges out of the HLA groove to compensate for its length.
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Probst-Kepper, M., Stroobant, V., Kridel, R., Gaugler, B., Landry, C., Brasseur, F., Cosyns, J.-P., Weynand, B., Boon, T., & Van den Eynde, B. (2001). An alternative open reading frame of the human macrophage colony-stimulating factor gene is independently translated and codes for an antigenic peptide of 14 amino acids recognized by tumor-infiltrating CD8 T lymphocytes. The Journal of Experimental Medicine, 193(10), 1189-1198. https://doi.org/10.1084/jem.193.10.1189 (Original work published 2001)