title: IRES-dependent translation of the long non coding RNA meloe in melanoma cells produces the most immunogenic MELOE antigens.
abstract: MELOE-1 and MELOE-2, two highly specific melanoma antigens involved in T cell immunosurveillance are produced by IRES-dependent translation of the long « non coding » and polycistronic RNA, meloe. In the present study, we document the expression of an additional ORF, MELOE-3, located in the 5' region of meloe. Data from in vitro translation experiments and transfection of melanoma cells with bicistronic vectors documented that MELOE-3 is exclusively translated by the classical cap-dependent pathway. Using a sensitive tandem mass spectrometry technique, we detected the presence of MELOE-3 in total lysates of both melanoma cells and normal melanocytes. This contrasts with our previous observation of the melanoma-restricted expression of MELOE-1 and MELOE-2. Furthermore, in vitro stimulation of PBMC from 6 healthy donors with overlapping peptides from MELOE-1 or MELOE-3 revealed a very scarce MELOE-3 specific T cell repertoire as compared to the abundant repertoire observed against MELOE-1. The poor immunogenicity of MELOE-3 and its expression in melanocytes is consistent with an immune tolerance towards a physiologically expressed protein. In contrast, melanoma-restricted expression of IRES-dependent MELOE-1 may explain its high immunogenicity. In conclusion, within the MELOE family, IRES-dependent antigens represent the best T cell targets for immunotherapy of melanoma.
authors.affiliation: CRCNA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Charpentier
authors.affiliation: UMR INRA 1280, CHU, Nantes, France.|West Human Nutrition Research Center, CHU, Nantes, France.
authors.forename: Mikael
authors.initials: M
authors.lastname: Croyal
authors.affiliation: CRCNA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Carbonnelle
authors.affiliation: CRCNA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Fortun
authors.affiliation: CRCNA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.|CHU, Nantes, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Florenceau
authors.affiliation: CRCNA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rabu
authors.affiliation: UMR INRA 1280, CHU, Nantes, France.|West Human Nutrition Research Center, CHU, Nantes, France.|CHU, Nantes, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Krempf
authors.affiliation: CRCNA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.|CHU, Nantes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labarrière
authors.affiliation: CRCNA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.
authors.forename: François
authors.initials: F
authors.lastname: Lang
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D000067556:Internal Ribosome Entry Sites / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics*; D014176:Protein Biosynthesis; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000067556:Internal Ribosome Entry Sites; C533520:MELOE-1 antigen, human; C547554:MELOE-2 antigen, human; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding
keywords: IRES; immunotherapy; long non coding RNA; melanoma; tumor antigens