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致关节炎性T细胞克隆的T细胞受体特异性克隆型抗体的产生与特性分析——佐剂性关节炎研究

Generation and characterization of a clonotypic antibody specific for the T cell receptor of an arthritogenic T cell clone--studies in adjuvant arthritis.

作者信息

van Tienhoven E A, Steenbakkers P G, Veenstra J G, van Kooten P J, van der Cammen M J, Broeren C P, van Eden W

机构信息

Institute of Infectious Diseases and Immunology, Department of Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

出版信息

J Autoimmun. 2000 Aug;15(1):1-8. doi: 10.1006/jaut.2000.0384.

Abstract

Adjuvant Arthritis (AA) can be induced by passive transfer of a T cell clone (A2b) derived from arthritic rats, specific for Heat Shock Protein 60, HSP60 176-190. Furthermore, a crucial role for T cells with HSP60 176-190 specificity in AA was shown by induction of tolerance using HSP60 176-190 or by immunization with an altered peptide ligand based on the same sequence. To study clonal expansion of A2b-like T cells during AA and to determine their role in AA induction, we generated a clonotypic antibody, 16C4, specific for the TCR of the A2b T cell clone (TCR AV11S1/BV18). This antibody stained A2b T cells in flow cytometry experiments, induced proliferation of A2b cells when fixed on a solid support, and inhibited antigen-induced A2b proliferation when added in solution. A2b-like T cells were detected in a low frequency in lymphoid organs of arthritic rats. Thus, as in vivo administration of 16C4 did not inhibit AA, cells containing the determinant recognized by 16C4 are possibly not the sole contributors to AA development. Furthermore, epitope specific interventions by antigen administration may be possible even in cases where the epitope specific T cell clonotype is of low frequency.

摘要

佐剂性关节炎(AA)可通过被动转移源自关节炎大鼠的T细胞克隆(A2b)来诱导,该克隆对热休克蛋白60(HSP60 176 - 190)具有特异性。此外,使用HSP60 176 - 190诱导耐受性或用基于相同序列的改变肽配体进行免疫,表明具有HSP60 176 - 190特异性的T细胞在AA中起关键作用。为了研究AA期间A2b样T细胞的克隆扩增并确定它们在AA诱导中的作用,我们制备了一种针对A2b T细胞克隆(TCR AV11S1/BV18)的TCR的克隆型抗体16C4。在流式细胞术实验中,该抗体可对A2b T细胞进行染色,固定在固体支持物上时可诱导A2b细胞增殖,加入溶液中时可抑制抗原诱导的A2b增殖。在关节炎大鼠的淋巴器官中检测到低频的A2b样T细胞。因此,由于体内给予16C4并未抑制AA,含有16C4识别的决定簇的细胞可能不是AA发展的唯一促成因素。此外,即使在表位特异性T细胞克隆型频率较低的情况下,通过给予抗原进行表位特异性干预也可能是可行的。

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