摘要
CD6的免疫疗法治疗银屑病和类风湿性关节炎已进入临床试验阶段并取得了明显的进展,单克隆抗体靶向CD6已用于自身免疫和炎症反应的动物模型并且效果良好。然而,CD6单抗治疗的作用方式从未被理解,其充满了不确定性,对CD6的机制和生物功能也充满了争议。CD6最初被发现能刺激受体T淋巴细胞,最近的研究表明,CD6可以调节早期以及后期的T细胞反应。同时,与CD6的粘附性对免疫突触的建立和稳定的贡献相反,实际触发CD6可能诱导T淋巴细胞的抗增殖信号。CD6有一个特别长的胞质尾,其基因将发生特殊的激活依赖剪模式。这一方面可以决定CD6蛋白质是否能结合其配体,另一方面包括或排除传导积极或消极信号的细胞内序列。本文讨论了通过CD6和在能定义T细胞表面分子的双重作用的情况下信号传导性质的多个方面。
关键词: CD6,免疫突触,T淋巴细胞活化,受体抑制剂,选择性剪接,免疫治疗
Current Drug Targets
Title:Tuning T Cell Activation: The Function of CD6 At the Immunological Synapse and in T Cell Responses
Volume: 17 Issue: 6
Author(s): Rita F. Santos, Liliana Oliveira and Alexandre M. Carmo
Affiliation:
关键词: CD6,免疫突触,T淋巴细胞活化,受体抑制剂,选择性剪接,免疫治疗
摘要: CD6 immunotherapy to treat psoriasis and rheumatoid arthritis has reached the clinical trial stage with apparent success, and targeting CD6 with mAbs is being used in several animal models of autoimmunity and neuroinflammation with promising indications. However, the mode of action of the therapeutic CD6 mAbs is far from being understood, reflecting the uncertainties and controversy surrounding the mechanistic and biological functions of CD6. Initially regarded as a co-stimulatory receptor of T lymphocytes, recent studies suggest that CD6 can instead modulate early as well as late T cell responses. Also, opposing the contribution of CD6 adhesiveness in the establishment and stabilization of immunological synapses, the actual triggering of CD6 might induce anti-proliferative signals to the T lymphocyte. CD6 has an unusually long cytoplasmic tail and its gene undergoes peculiar patterns of activation-dependent alternative splicing that can on one hand determine whether or not the CD6 protein binds to its ligand, and on the other include or exclude intracellular sequences that may transduce positive or negative signaling. In this review we discuss the multiple aspects that determine the nature of the signals transmitted via CD6 and the context that may define a dual role for this important T cell surface molecule.
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Cite this article as:
Rita F. Santos, Liliana Oliveira and Alexandre M. Carmo , Tuning T Cell Activation: The Function of CD6 At the Immunological Synapse and in T Cell Responses, Current Drug Targets 2016; 17 (6) . https://dx.doi.org/10.2174/1389450116666150531152439
DOI https://dx.doi.org/10.2174/1389450116666150531152439 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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