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人类抗体中的调节性T细胞表位含量在成熟过程中下降

Andres H Gutierrez¹, Frances E Terry¹, Amy S Rosenberg¹

¹EpiVax, Inc., Providence, RI, United States.

Frontiers in immunology

|May 2, 2025

概括

调节性T细胞表位 (Tregitopes) 在抗体成熟过程中随着体质突变 (SHM) 的增加而减少. 这种Tregitope耗尽表明调节性T细胞活性下降,支持抗异型反应.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
抗体工程抗体工程

背景情况:

淋巴卵泡中的抗体成熟通过代突变和B细胞扩张增强了抗体结合亲和力.
T细胞通过识别MHC-II.II上B细胞呈现的表位体,在抗体成熟中发挥关键作用.
之前的研究表明,B细胞受体 (BCR) 衍生的HLA-DR表位减少,随着体质突变 (SHM) 的增加.

研究的目的:

为了研究在抗体成熟过程中,供体特异性HLA-DR T细胞表位的动态.
分析调节性T细胞表位 (Tregitopes),潜在耐受性表位和具有SHM的潜在效应性T细胞表位的变化.
评估SHM对T细胞表位表型 (调节性与效应性) 的影响.

主要方法:

来自四名健康人体捐赠者的抗体库的分析.
查供体特定的HLA-DR T细胞表位,并将其分类为Tregitopes,耐受性和效应性表位.
在表位素含量,SHM水平和抗体同型 (IgM,IgA,IgG) 之间的相关性分析.

主要成果:

随着SHM的增加,基含量显著下降,这表明在抗体成熟期间的去除.
潜在耐受性或耐受性T细胞表位也随着SHM进展而减少.
相比之下,潜在的T因子表皮质含量增加了SHM;Tregitope耗尽是频繁的,并与类交换和成熟到等离子体相关联.

结论:

特雷吉托普枯竭与SHM的相关性表明,在抗体成熟和同型切换过程中,调节性T细胞的作用下降.
这种降低Tregitopes可能有助于产生反型反应.
由SHM引入的突变可以改变Tregitope HLA-DR结合亲缘关系,影响T细胞的识别.

关键词:

B细胞成熟的过程 B细胞受体 (BCR) 是一种B细胞受体.在 HLA-DR T 细胞表位上.在Tregitopes中使用.抗体谱的抗体谱是什么胚芽中心 (GC)调节性T细胞表观.身体突变 (SHM) 是一种身体突变.

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