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International Immunology, Vol. 15, No. 12, pp. 1415-1421, December 2003
© 2003 Japanese Society for Immunology

IFN-{alpha} mediates the up-regulation of HLA class I on melanoma cells without switching proteasome to immunoproteasome

Giuliana Cangemi1, Barbara Morandi2, Antonella D‘Agostino1, Cristiano Peri1, Romana Conte2, Gianluca Damonte3, Guido Ferlazzo1, Roberto Biassoni4 and Giovanni Melioli1

1 Laboratorio di Analisi, Istituto Giannina Gaslini, 16148 Genoa, Italy 2 Laboratorio di Immunologia, Istituto Nazionale per la Ricerca sul Cancro, Genoa, 16132 Italy 3 Sezione di Biochimica, Dipartimento di Medicina Sperimentale, Università di Genova, Genoa, 16132 Italy 4 Laboratorio di Medicina Molecolare, Istituto Giannina Gaslini, 16148 Genoa, Italy

Correspondence to: G. Melioli; E-mail: giovannimelioli{at}ospedale-gaslini.ge.it
Transmitting editor: L. Moretta

Treatment of melanoma cell lines with IFN-{gamma} induces the switch from proteasome (PS) to immunoproteasome (iPS). This finding has profound implications for the immunobiology of melanoma cells since certain peptides (such as Melan-Amart127–35) are cleaved differently by iPS, thus implying a different ability to be presented by HLA class I molecules. IFN-{alpha} is a cytokine not only produced during infectious diseases, but also used in the treatment of certain cancers. Nevertheless, the effects of IFN-{alpha} on the switch of PS to iPS are largely unknown. A comparison of the effect of both IFN-{alpha} and IFN-{gamma} was thus carried out on melanoma cell lines. RT-PCR showed that mRNA for iPS subunits (i.e. LMP-2, LMP-7 and MECL-1) was detectable both in untreated and IFN-treated melanoma cells. Immunoblotting analysis revealed that while IFN-{gamma} was able to consistently induce the switch from PS to iPS, IFN-{alpha} treatment did not, possibly due to post-transcriptional event(s) blocking the expression of iPS-specific subunits. Finally, Melan-Amart127–35 peptide was found only in the HPLC-MS spectra from both untreated and IFN-{alpha}-treated cells, but not upon IFN-{gamma} treatment. Altogether, these data demonstrate that IFN-{alpha} does not induce the switch from PS to iPS.

Keywords: IFN, HLA, peptide, proteasome


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