A critical regulatory role for the cytoplasmic domain of CD28 in ligand binding in naive T cells  

CD28胞内域对初始T细胞CD28受体与配体结合具有关键调控作用

作　　者：Cheng-Rui Qian Fan Xia Anne-Marie Sartre Anthony Formisano Sébastian Jaeger Jacques A.Nunès Xiao-Jun Guo Hai-Tao He 钱呈睿;夏凡;Anne-Marie Sartre;Anthony Formisano;Sébastian Jaeger;Jacques A.Nunès;郭晓君;何海涛(Aix Marseille Univ,CNRS,INSERM,CIML,13288 Marseille,France;Shanghai Blood Center,Shanghai 200051,China;Department of Radiation Oncology,Fudan University Shanghai Cancer Center,Shanghai 200032,China;Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China;Aix Marseille Univ,CNRS,INSERM,Institut Paoli-Calmettes,CRCM,13273 Marseille,France;Centre de Recherche en Cancérologie de Marseille,Immunology and Cancer,Equipe Labellisée Fondation pour la Recherche Médicale,13273 Marseille,France)

机构地区：[1]Aix Marseille Univ,CNRS,INSERM,CIML,13288 Marseille,France [2]Shanghai Blood Center,Shanghai 200051,China [3]Department of Radiation Oncology,Fudan University Shanghai Cancer Center,Shanghai 200032,China [4]Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China [5]Aix Marseille Univ,CNRS,INSERM,Institut Paoli-Calmettes,CRCM,13273 Marseille,France [6]Centre de Recherche en Cancérologie de Marseille,Immunology and Cancer,Equipe Labellisée Fondation pour la Recherche Médicale,13273 Marseille,France

出　　处：《Science Bulletin》2021年第2期107-110,M0003,共5页科学通报（英文版）

基　　金：supported by institutional grants from INSERM and CNRS and by specific grants from CNRS(CNRS IRP CHOLESTIM);the Agence Nationale de la Recherche(ANR-10-BLAN-1509;ANR-11-LABX-Investissement d’Avenir Labex-INFORM;ANR-17CE15-0032)。

摘　　要：T cell activation is a main component of adaptive immunity,which involves two types of signals transmitted by key immune receptors upon engagement with their respective ligands present on the antigen-presenting cells(APCs)[1].The first signal is induced via the T cell receptor(TCR)upon binding to antigenic peptide–major histocompatibility complex(pMHC);the second signal is induced via the costimulatory receptors,the prototype of which is CD28,which can bind to either B7-1(also known as CD80)or B7-2(also known as CD86)[2,3].初始T细胞活化是由T细胞受体(TCR)及共刺激分子与其配体结合引起的,其中CD28共刺激信号在促进初始T细胞的活化过程中起关键作用.本文研究了小鼠CD4^(+)T细胞中CD28与B7配体的结合活性在CD28介导的信号通路激活中的调控机制.结果发现虽然初始CD4^(+)T细胞表面CD28-B7的本底结合力很低,但当同步给予TCR刺激可触发CD28胞内域激酶SRC酪氨酸磷酸化,并由此显著增强CD28-B7的结合力.此外通过CD28胞内域缺失的小鼠模型,进一步验证CD28胞内结构域的存在是TCR刺激信号增强CD28-B7结合力的必要条件.据此,本研究证实CD28胞内域在其配体结合过程中承担了关键性的调控作用,并为TCR和CD28相互作用介导初始T细胞活化提供了新的证据.

关 键 词：初始T细胞 CD28 共刺激信号 酪氨酸磷酸化 T细胞活化 胞内域 共刺激分子 活化过程 

分 类 号：Q25[生物学—细胞生物学]