title: AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma.
abstract: AIRE is involved in susceptibility to melanoma perhaps regulating T cell immunity against melanoma antigens (MA). To address this issue, AIRE and MAGEB2 expressions were measured by real time PCR in medullary thymic epithelial cells (mTECs) from two strains of C57BL/6 mice bearing either T or C allelic variant of the rs1800522 AIRE SNP. Moreover, the extent of apoptosis induced by mTECs in MAGEB2-specific T cells and the susceptibility to in vivo melanoma B16F10 cell challenge were compared in the two mouse strains.The C allelic variant, protective in humans against melanoma, induced lower AIRE and MAGEB2 expression in C57BL/6 mouse mTECs than the T allele. Moreover, mTECs expressing the C allelic variant induced lower extent of apoptosis in MAGEB2-specific syngeneic T cells than mTECs bearing the T allelic variant (p < 0.05). Vaccination against MAGEB2 induced higher frequency of MAGEB2-specific CTL and exerted higher protective effect against melanoma development in mice bearing the CC AIRE genotype than in those bearing the TT one (p < 0.05). These findings show that allelic variants of one AIRE SNP may differentially shape the MA-specific T cell repertoire potentially influencing susceptibility to melanoma.
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Giuseppina
authors: G
authors: Conteduca
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.|Department of Internal Medicine, University of Genoa, Genoa, Italy.|IRCCS AOU San Martino - IST, Genoa, Italy.
authors: Daniela
authors: D
authors: Fenoglio
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Alessia
authors: A
authors: Parodi
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Florinda
authors: F
authors: Battaglia
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Francesca
authors: F
authors: Kalli
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Simone
authors: S
authors: Negrini
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Samuele
authors: S
authors: Tardito
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Francesca
authors: F
authors: Ferrera
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Annalisa
authors: A
authors: Salis
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Enrico
authors: E
authors: Millo
authors: Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy.
authors: Giuseppe
authors: G
authors: Pasquale
authors: Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy.
authors: Giusi
authors: G
authors: Barra
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Gianluca
authors: G
authors: Damonte
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.|Department of Internal Medicine, University of Genoa, Genoa, Italy.
authors: Francesco
authors: F
authors: Indiveri
authors: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Soldano
authors: S
authors: Ferrone
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.|Department of Internal Medicine, University of Genoa, Genoa, Italy.|IRCCS AOU San Martino - IST, Genoa, Italy.
authors: Gilberto
authors: G
authors: Filaci
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004847:Epithelial Cells; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008546:Melanoma, Experimental; D058950:Melanoma-Specific Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014157:Transcription Factors; D000096927:AIRE Protein; C072012:MAGEB2 protein, human; C512965:Mageb2 protein, mouse
keywords: AIRE; Immune response; Immunity; Immunology and Microbiology Section; MAGE; medullary thymic epithelial cells; single nucleotide polymorphism; tolerance