alpha-interferon treatment induces quantitative modifications of HLA classI-associated peptides eluted from cultured cancer cell lines

Interferons upregulate the expression of HLA class I antigens on cancer cel ls. Nevertheless, little is known about the panel of HLA class I antigen-as sociated peptides presented by recombinant alpha-interferon (r alpha-IFN)-t reated cells. For this reason, peptides were eluted from five cancer cell l ines (four melanoma and one non-small cell lung cancer) following treat men t with m-IFN. High-performance liquid chromatography (HPLC) profiles of the peptide fractions were compared with those obtained from untreated cells. No significant differences in peptide characteristics (detectable on the ba sis of retention times) were observed, but significant differences in terms of peptide quantities were observed. Mass spectrometry performed on HPLC p eaks allowed not only the detection of three different peptides (two derive d from the MAGE family of genes and one from the mart-1) both in untreated and in treated cells, but also gave an indication of the number of peptides within one HPLC peak. This data demonstrates that r alpha-IFN-treated cell s express a similar peptide pattern as untreated cells, with significant qu antitative differences. Interestingly, this finding also explains the highe r susceptibility to lysis (mediated by specific cytolytic lymphocytes, whic h recognize cancer cells in an HLA-restricted fashion) of r alpha-IFN-treat ed cells.