Autopathogenic T helper cell type 1 (Th1) and protective Th2 clones differ in their recognition of the autoantigenic peptide of myelin proteolipid protein.
Autopathogenic T helper cell type 1 (Th1) and protective Th2 clones differ in their recognition of the autoantigenic peptide of myelin proteolipid protein.
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DOI：
10.1084/jem.186.6.867
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发表时间：
1997-09-15
期刊：
影响因子：
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通讯作者：
Kuchroo VK
中科院分区：
文献类型：
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作者：
Das MP;Nicholson LB;Greer JM;Kuchroo VK
我们先前产生了一组T辅助细胞1（Th 1）克隆特异性的致脑炎肽髓鞘蛋白脂质蛋白（PLP）肽139-151（HSLGKWLGHPDKF），诱导实验性自身免疫性脑脊髓炎（EAE）过继转移。尽管它们的T细胞受体（TCR）基因使用存在差异，但所有这些Th 1克隆都需要W144作为活化的主要和最关键的TCR接触残基。在本研究中，我们测定了一组对PLP肽139 - 151特异的Th 2/Th 0克隆的TCR接触残基，所述克隆通过用具有抗B7-1抗体的PLP 139-151肽免疫或通过用改变的肽Q144免疫而产生。使用丙氨酸取代的肽类似物的天然PLP肽，我们表明，Th 2克隆已转移其主要接触残基的NH 2-末端的肽。这些Th 2细胞不显示对W144的任何依赖性，但显示对L141/G142作为其主要TCR接触残基的关键需求。因此，与不增殖为A144取代肽的Th 1克隆相反，Th 2克隆耐受144位的取代并增殖为A144肽。这种替代的A144反应性库似乎在调节对PLP 139-151的自身免疫应答中具有关键作用，因为用A144预免疫以扩大L141/G142反应性库保护小鼠免于发展用天然PLP 139-151肽诱导的EAE。这些数据表明，对相同自身抗原表位特异性的两种不同T细胞库之间的平衡可以决定疾病表型，即，对自身免疫性疾病的抵抗力或易感性。
We previously generated a panel of T helper cell 1 (Th1) clones specific for an encephalitogenic peptide of myelin proteolipid protein (PLP) peptide 139–151 (HSLGKWLGHPDKF) that induces experimental autoimmune encephalomyelitis (EAE) upon adoptive transfer. In spite of the differences in their T cell receptor (TCR) gene usage, all these Th1 clones required W144 as the primary and most critical TCR contact residue for the activation. In this study, we determined the TCR contact residues of a panel of Th2/Th0 clones specific for the PLP peptide 139–151 generated either by immunization with the PLP 139–151 peptide with anti– B7-1 antibody or by immunization with an altered peptide Q144. Using alanine-substituted peptide analogues of the native PLP peptide, we show that the Th2 clones have shifted their primary contact residue to the NH2-terminal end of the peptide. These Th2 cells do not show any dependence on the W144, but show a critical requirement for L141/G142 as their major TCR contact residue. Thus, in contrast with the Th1 clones that did not proliferate to A144-substituted peptide, the Th2 clones tolerated a substitution at position 144 and proliferated to A144 peptide. This alternative A144 reactive repertoire appears to have a critical role in the regulation of autoimmune response to PLP 139–151 because preimmunization with A144 to expand the L141/G142-reactive repertoire protects mice from developing EAE induced with the native PLP 139–151 peptide. These data suggest that a balance between two different T cell repertoires specific for same autoantigenic epitope can determine disease phenotype, i.e., resistance or susceptibility to an autoimmune disease.