IRES-dependent translation of the long non coding RNA meloe in melanoma cells produces the most immunogenic MELOE antigens
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Maud Charpentier1, Mikael Croyal2,3, Delphine Carbonnelle1, Agnès Fortun1, Laetitia Florenceau1,4, Catherine Rabu1, Michel Krempf2,3,4, Nathalie Labarrière1,4, François Lang1
1CRCNA, INSERM, CNRS, Université d’Angers, Université de Nantes, Nantes, France
2UMR INRA 1280, CHU, Nantes, France
3West Human Nutrition Research Center, CHU, Nantes, France
4CHU, Nantes, France
François Lang, email: firstname.lastname@example.org
Keywords: melanoma, IRES, long non coding RNA, tumor antigens, immunotherapy
Received: June 07, 2016 Accepted: July 20, 2016 Published: July 29, 2016
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.
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