TSH receptor sequences recognized by CD4+ T cells in Graves' disease patients and healthy controls.
TSH receptor sequences recognized by CD4+ T cells in Graves' disease patients and healthy controls.
复制标题
格雷夫斯病患者和健康对照者的 CD4 T 细胞识别 TSH 受体序列。
DOI：
10.1006/jaut.1995.0051
复制
发表时间：
1995
影响因子：
12.8
通讯作者：
Conti-Fine,BM
中科院分区：
文献类型：
--
作者：
Kellermann,SA;McCormick,DJ;Freeman,SL;Morris,JC;Conti-Fine,BM
29个重叠的合成肽，长20个残基，代表了人促甲状腺激素受体（hTSHr）的整个细胞外序列，用于检测格雷夫斯病患者和健康受试者的CD4+T淋巴细胞表位库。这些肽被用于增殖和检测hTSHr表位特异性的短期CD4+T细胞系，以及直接检测CD8+缺失、CD4+富集的外周血淋巴细胞。分析短期CD4+T细胞系和CD8+缺失的外周血淋巴细胞对单个肽的反应显示，15名患者中的14名和10名对照中的9名对至少一种hTSHr肽有反应。没有共同的反应模式，也没有hTSHr序列的任何区域被主要识别。患者和对照组都能识别出几种多肽。这些结果支持了对hTSHr的免疫耐受是由于潜在的自身反应性CD4+T细胞的外周耐受，而不是它们的克隆缺失。健康个体中存在自我反应性、htshrr特异性CD4+T细胞，这意味着这些细胞不是永久性失能的，因为它们可以在体外被激活。
Twenty-nine overlapping synthetic peptides, twenty residues long, representing the entire extracellular sequence of the human thyroid stimulating hormone receptor (hTSHr), were used to test the epitope repertoire of CD4+T lymphocytes from patients with Graves' disease and from healthy subjects. The peptides were used to propagate and test short term CD4+T cell lines specific for hTSHr epitopes, and to directly test CD8+depleted, CD4+enriched peripheral blood lymphocytes. Analysis of the response of short-term CD4+T cell lines and CD8+depleted peripheral blood lymphocytes to the individual peptides revealed that 14 of the 15 patients and nine of the ten controls responded to at least one hTSHr peptide. There was no common response pattern, nor any region of the hTSHr sequence that was predominantly recognized. Several peptides were recognized by both patients and controls. These results support the notion that immunological tolerance to hTSHr is due to peripheral tolerance of potentially autoreactive CD4+T cells, not their clonal deletion. The presence of self-reactive, hTSHr-specific CD4+T cells in healthy individuals implies that these cells are not permanently anergized, since they can be activatedin vitro.