Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin.
Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin.
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DOI：
10.1038/gene.2009.108
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发表时间：
2010-03
影响因子：
5
通讯作者：
Nepom, G. T.
中科院分区：
文献类型：
--
作者：
Durinovic-Bello, I.;Wu, R. P.;Gersuk, V. H.;Sanda, S.;Shilling, H. G.;Nepom, G. T.
Immune responses to autoantigens are in part controlled by deletion of autoreactive cells through genetically regulated selection mechanisms. We have directly analyzed peripheral CD4+ proinsulin (PI) 76–90 (SLQPLALEGSLQKRG)-specific T cells using soluble fluorescent major histocompatibility complex class II tetramers. Subjects with type I diabetes and healthy controls with high levels of peripheral proinsulin-specific T cells were characterized by the presence of a disease-susceptible polymorphism in the insulin variable number of tandem repeats (INS-VNTR) gene. Conversely, subjects with a ‘protective' polymorphism in the INS-VNTR gene had nearly undetectable levels of proinsulin tetramer-positive T cells. These results strongly imply a direct relationship between genetic control of autoantigen expression and peripheral autoreactivity, in which proinsulin genotype restricts the quantity and quality of the potential T-cell response. Using a modified tetramer to isolate low-avidity proinsulin-specific T cells from subjects with the susceptible genotype, transcript arrays identified several induced pro-apoptotic genes in the control, but not diabetic subjects, likely representing a second peripheral mechanism for maintenance of tolerance to self antigens.
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影响因子：
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作者：
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DOI：
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