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Studi di immunogenicità in modelli murini Laura Pisapia Giovanna Del Pozzo Napoli, 27 Giugno 2013
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Corso C. et al. EBP1 and DRBP76/NF90 binding proteins are included in the Major Histocompatibility Complex Class II RNA operon. 2011 N.A.R Sep 1;39(16):7263-75. Pisapia L. et al. Co-regulated expression of alpha and beta mRNAs encoding HLA-DR surface heterodimers is mediated by the MHCII RNA operon. 2013 N.A.R. Apr1;41(6):3772-86. MHC class II RNA Operon
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EBP1 Identified as ErbB3 binding protein, is the human homologue of mouse cell-cycle regulated protein p38-2G4 In carcinoma cell lines p48 isoform functions as tumor suppressor In PC12 and glioblastoma p48 works as oncogene, while p42 isoform is a tumor suppressor Translational control: in the cytoplasm is associated to 80S ribosomes and polysomes inhibits translation of AR mRNA Transcriptional repressor: Inhibits transcription of E2F regulated promoters by recruiting HDAC2/Rb/Sin3A comple x RNA binding protein: influences bcl2 stability, promotes decay of androgen receptor mRNA, binds UTRs of MHCII p48 and p42 isoforms
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p48 isoform binds 5’ and 3’UTR of MHCII mRNAs The over expression of p48 isoform determines an up- regulation of MHC Class II in different cancer cell lines Over-expression of p42 and p48 EBP1 influences MHCII amount
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OT-II MOUSE OT-I MOUSE Spleen T CD4+ magnetic selection T CD8+ magnetic selection B16-OVAa and CD8+ co-culture B16-OVA and CD4+ co-culture Melanoma B16-OVA CD8+ T cell CD4+ T cell CD8 OVA 257–264 (SIINFEKL) peptide CD4 OVA 323–339 (ISQAVHAAHAEINEAGR) peptide CD8+ CFSE labelling CD4+ CFSE labelling T cells activation and proliferation are demonstrated by the decrease of CFSE labelling CFSE
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