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外来抗原中的自身表位:T细胞与自身抗原

[Body's Own Epitopes among Foreign Ones: T Cells and Autoantigens].

作者信息

Shilov E S

机构信息

Immunology Department, Moscow State University, Moscow, 119234 Russia.

出版信息

Mol Biol (Mosk). 2019 Sep-Oct;53(5):849-859. doi: 10.1134/S0026898419050148.

Abstract

T cells play a key role in adaptive immunity reactions, recognizing antigens using variable TCRs. Functional TCR subunit genes are formed by somatic rearrangement, and some of the resulting TCRs recognize autoantigens, the body's own molecules. The autoreactive T cells that carry such TCRs pose a threat of inducing immune reactions against their own organism. In the course of the immune system's development, some autoreactive T lymphocytes are eliminated by apoptosis, some differentiate into immunosuppressive regulatory T cells, which support immunological tolerance to autoantigens, and the rest fall into a non-functional state of anergy. Suppression of effector T cells by regulatory T cells is mediated by immunosuppressive cytokines and costimulatory molecules, depletion of stimulating IL-2, removal of autoreactive peptides together with MHC molecules, and in other ways. Impairment of self-tolerance leads to autoimmune diseases. However, the loss of immunological tolerance can be employed in tumor treatment, allowing immunotherapy and the use of the potential of autoreactive effector T cells. The fact that the efficacious immunotherapy of tumors is often accompanied by adverse autoimmune reactions currently seems to be the inevitable price paid by using this approach.

摘要

T细胞在适应性免疫反应中发挥关键作用,通过可变的TCR识别抗原。功能性TCR亚基基因通过体细胞重排形成,其中一些产生的TCR识别自身抗原,即机体自身的分子。携带此类TCR的自身反应性T细胞构成了引发针对自身机体免疫反应的威胁。在免疫系统发育过程中,一些自身反应性T淋巴细胞通过凋亡被清除,一些分化为免疫抑制性调节性T细胞,后者支持对自身抗原的免疫耐受,其余的则进入无功能的失能状态。调节性T细胞对效应T细胞的抑制作用由免疫抑制性细胞因子和共刺激分子介导,通过消耗刺激性白细胞介素-2、与MHC分子一起清除自身反应性肽段以及其他方式来实现。自身耐受的受损会导致自身免疫性疾病。然而,免疫耐受的丧失可用于肿瘤治疗,从而实现免疫治疗并利用自身反应性效应T细胞的潜能。目前,肿瘤的有效免疫治疗常常伴随着不良的自身免疫反应,这似乎是采用这种方法不可避免要付出的代价。

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