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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.

Original publication

DOI

10.1084/jem.193.10.1189

Type

Journal article

Journal

J Exp Med

Publication Date

21/05/2001

Volume

193

Pages

1189 - 1198

Keywords

Amino Acid Sequence, Antigens, Neoplasm, Base Sequence, Carcinoma, Renal Cell, Cytotoxicity, Immunologic, HLA-B35 Antigen, Humans, Kidney Neoplasms, Lymphocytes, Tumor-Infiltrating, Macrophage Colony-Stimulating Factor, Molecular Sequence Data, Open Reading Frames, Peptides, Protein Biosynthesis, T-Lymphocytes, Cytotoxic