Degenerate recognition and response of human CD4+ Th cell clones: implications for basic and applied immunology.
Degenerate recognition and response of human CD4+ Th cell clones: implications for basic and applied immunology.
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DOI：
10.1016/j.molimm.2003.11.009
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发表时间：
2004-02
影响因子：
3.6
通讯作者：
Y. Nishimura;Yu-zhen Chen;Y. Uemura;Yoshihiko Tanaka;Hirotake Tsukamoto;Takayuki Kanai;H. Yokomizo;Chyuns Yun;T. Matsuoka;A. Irie;S. Matsushita
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文献类型：
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作者：
Y. Nishimura;Yu-zhen Chen;Y. Uemura;Yoshihiko Tanaka;Hirotake Tsukamoto;Takayuki Kanai;H. Yokomizo;Chyuns Yun;T. Matsuoka;A. Irie;S. Matsushita
曾经认为T细胞应答是全有或全无类型的事件，但最近的研究清楚地表明，T细胞在识别T细胞受体（TCR）的改变的配体时显示出许多不同类型的活化。在这篇综述中，我们总结了我们最近的研究结果对人类CD 4+辅助性T（Th）细胞克隆改变肽配体（APL）的反应，肽携带单个或多个残基取代的抗原肽。广泛的分析表明，TCR拮抗和部分激动作用经常被抗原肽的特定氨基酸残基取代的APL刺激所观察到。我们观察到独特的部分激动性APLs诱导T细胞存活时间延长而无细胞增殖。超激动剂APLs刺激Th细胞克隆对肿瘤相关抗原的反应性增强增殖和细胞因子的产生。另一种APL诱导抗原呈递细胞产生白细胞介素-12的增强，以及随后对过敏原反应的T细胞产生IFN-γ的增强。通过利用由突变的不变链基因产生的HLA-DR限制性T细胞表位文库，揭示了人Th细胞克隆识别在抗原肽中具有多个和同时的氨基酸取代的更多样化的肽阵列。APLs还诱导改变的细胞内信号传导事件，包括细胞内钙增加和信号分子的磷酸化。这些信息提供了关于人Th细胞的抗原识别和随后的激活的特征的基本知识，以及通过APLs操纵人Th细胞应答的新方法，作为抗原特异性免疫增强或免疫抑制治疗的可能候选者。
It was once considered that the T cell response is an all or nothing type event, but recent studies have clearly indicated that T cells show many different types of activation in recognition of altered ligands for T cell receptors (TCR). In this review, we summarize our recent findings on the response of human CD4+helper T (Th) cell clones to altered peptide ligands (APL); peptides carrying single or multiple residue substitutions in antigenic peptides. The extensive analyses revealed that TCR-antagonism and partial agonism are frequently observed by the stimulation with APLs substituted at particular amino acid residues of antigenic peptides. We observed unique partially agonistic APLs inducing prolongation of T cell survival without cell proliferation. Superagonistic APLs stimulated enhanced proliferation and production of cytokines in Th cell clones reactive to tumor-associated antigens. The other APL induced enhanced production of interleukin-12 by antigen presenting cells and subsequent enhancement of IFN-γ production by T cells reactive to allergens. By utilizing an HLA-DR-restricted T cell epitope library generated by mutated invariant chain genes, it was revealed that human Th cell clones recognize a more diverse array of peptides with multiple and simultaneous amino acid substitutions in an antigenic peptide. APLs also induced altered intracellular signaling events including intracellular calcium increase and phosphorylation of signaling molecules. This information provides basic knowledge regarding the characteristics of antigen recognition by human Th cells and the subsequent activation, and a novel method for manipulation of human Th cell responses by APLs, as a possible candidate for antigen-specific immuno-potentiating or immunosuppressive therapy.