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.
| Original language | English |
|---|---|
| Pages (from-to) | 60872-60884 |
| Number of pages | 13 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 38 |
| DOIs | |
| Publication status | Published - 2016 |
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Keywords
- AIRE
- Immune response
- Immunity
- Immunology and Microbiology Section
- MAGE
- Medullary thymic epithelial cells
- Single nucleotide polymorphism
- Tolerance
ASJC Scopus subject areas
- Oncology
Cite this
AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma. / Conteduca, Giuseppina; Fenoglio, Daniela; Parodi, Alessia; Battaglia, Florinda; Kalli, Francesca; Negrini, Simone; Tardito, Samuele; Ferrera, Francesca; Salis, Annalisa; Millo, Enrico; Pasquale, Giuseppe; Barra, Giusi; Damonte, Gianluca; Indiveri, Francesco; Ferrone, Soldano; Filaci, Gilberto.
In: Oncotarget, Vol. 7, No. 38, 2016, p. 60872-60884.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma
AU - Conteduca, Giuseppina
AU - Fenoglio, Daniela
AU - Parodi, Alessia
AU - Battaglia, Florinda
AU - Kalli, Francesca
AU - Negrini, Simone
AU - Tardito, Samuele
AU - Ferrera, Francesca
AU - Salis, Annalisa
AU - Millo, Enrico
AU - Pasquale, Giuseppe
AU - Barra, Giusi
AU - Damonte, Gianluca
AU - Indiveri, Francesco
AU - Ferrone, Soldano
AU - Filaci, Gilberto
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - AIRE
KW - Immune response
KW - Immunity
KW - Immunology and Microbiology Section
KW - MAGE
KW - Medullary thymic epithelial cells
KW - Single nucleotide polymorphism
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=84992520705&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992520705&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.11506
DO - 10.18632/oncotarget.11506
M3 - Article
VL - 7
SP - 60872
EP - 60884
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 38
ER -