Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity.
Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity.
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易感 MHC 等位基因（而非背景基因）选择自身免疫 T 细胞反应性。
DOI：
10.1172/jci18337
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Tey
中科院分区：
文献类型：
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作者：
Stratmann,Thomas;Martin-Orozco,Natalia;Mallet-Designe,Valerie;Poirot,Laurent;McGavern,Dorian;Losyev,Grigoriy;Dobbs,CathleenM;Oldstone,MichaelBA;Yoshida,Kenji;Kikutani,Hitoshi;Mathis,Diane;Benoist,Christophe;Haskins,Kathryn;Tey
为了检测和表征糖尿病易感NOD小鼠中的自身反应性T细胞，我们开发了一种对BDC-2.5 T细胞受体具有高亲和力的多聚体MHC试剂，该受体对胰腺自身抗原具有反应性。在NOD小鼠中检测到识别相同MHC/肽靶标的不同T细胞群体。这些T细胞在胸腺中以令人惊讶的高频率被阳性选择并输出到外周。它们在胰腺淋巴结中特异性活化，证明了重演BDC-2.5细胞的自身免疫特异性。在与NOD共享H-2g 7 MHC单倍型但携带糖尿病抗性背景基因的小鼠品系中也观察到这些现象。因此，在MHC的易感单倍型似乎是选择和出现自身反应性T细胞所需的唯一元素，而不需要来自NOD基因组的其他致糖尿病基因座。
To detect and characterize autoreactive T cells in diabetes-prone NOD mice, we have developed a multimeric MHC reagent with high affinity for the BDC-2.5 T cell receptor, which is reactive against a pancreatic autoantigen. A distinct population of T cells is detected in NOD mice that recognizes the same MHC/peptide target. These T cells are positively selected in the thymus at a surprisingly high frequency and exported to the periphery. They are activated specifically in the pancreatic LNs, demonstrating an autoimmune specificity that recapitulates that of the BDC-2.5 cell. These phenomena are also observed in mouse lines that share with NOD the H-2g7MHC haplotype but carry diabetes-resistance background genes. Thus, a susceptible haplotype at the MHC seems to be the only element required for the selection and emergence of autoreactive T cells, without requiring other diabetogenic loci from the NOD genome.