Reference : AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to m...
Scientific journals : Article
Human health sciences : Oncology
AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma
Conteduca, Giuseppina mailto [Université de Liège > > GIGA-R : Hématologie >]
Impact Journals
[en] AIRE ; MAGE ; mTEC
[en] 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.
CEBR, Centre of Excellence for Biomedical Research
AIRC (Italian Foundation for Cancer Research), grant from MIUR, PRIN
Immunotherapy anti tumoral

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