Oncotarget

Research Papers: Immunology:

AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma

Giuseppina Conteduca, Daniela Fenoglio, Alessia Parodi, Florinda Battaglia, Francesca Kalli, Simone Negrini, Samuele Tardito, Francesca Ferrera, Annalisa Salis, Enrico Millo, Giuseppe Pasquale, Giusi Barra, Gianluca Damonte, Francesco Indiveri, Soldano Ferrone and Gilberto Filaci _

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Oncotarget. 2016; 7:60872-60884. https://doi.org/10.18632/oncotarget.11506

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Abstract

Giuseppina Conteduca1, Daniela Fenoglio1,2,3, Alessia Parodi1, Florinda Battaglia1, Francesca Kalli1, Simone Negrini1, Samuele Tardito1, Francesca Ferrera1, Annalisa Salis1, Enrico Millo1, Giuseppe Pasquale4, Giusi Barra4, Gianluca Damonte1, Francesco Indiveri1,2, Soldano Ferrone5,* and Gilberto Filaci1,2,3,*

1 Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy

2 Department of Internal Medicine, University of Genoa, Genoa, Italy

3 IRCCS AOU San Martino – IST, Genoa, Italy

4 Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy

5 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

* These authors have contributed equally to the manuscript

Correspondence to:

Gilberto Filaci, email:

Keywords: AIRE, MAGE, medullary thymic epithelial cells, single nucleotide polymorphism, tolerance, Immunology and Microbiology Section, Immune response, Immunity

Received: January 27, 2016 Accepted: August 08, 2016 Published: August 22, 2016

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.


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