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生成一种针对结核分枝杆菌(Mtb)热休克蛋白(HSP)16kDa 抗原的 T 细胞受体(TCR)样单域抗体(sDAb),该抗原由人类白细胞抗原(HLA)-A*02 呈递。

Generation of a T cell receptor (TCR)-like single domain antibody (sDAb) against a Mycobacterium Tuberculosis (Mtb) heat shock protein (HSP) 16kDa antigen presented by Human Leukocyte Antigen (HLA)-A*02.

机构信息

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.

School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

出版信息

Mol Immunol. 2018 Sep;101:189-196. doi: 10.1016/j.molimm.2018.07.001. Epub 2018 Jul 4.

Abstract

The discovery of heat shock protein 16 kDa antigen protein has deepen the understanding of latent tuberculosis since it was found to be primarily expressed by Mycobacterium tuberculosis during latent phase leading to the rapid optimization and development in terms of diagnosis and therapeutics. Recently, T cell receptor-like antibody has been explored extensively targeting various diseases due to its dual functionality (T cell receptor and antibody). In this study, a TCR-like domain antibody (A2/Ab) with the binding capacity to Mtb heat shock protein (HSP) 16 kDa antigen presented by major histocompatible complex (MHC) HLA-A*02 was successfully generated via biopanning against human domain antibody library. The generated antibody (A2/Ab) exhibited strong functionality and binding capacity against the target assuring the findings of this study to be beneficial for the development of latent tuberculosis diagnosis and immunotherapeutics in future.

摘要

热休克蛋白 16kDa 抗原蛋白的发现加深了对潜伏性结核的认识,因为它主要在潜伏期的结核分枝杆菌中表达,从而导致诊断和治疗方面的快速优化和发展。最近,由于 T 细胞受体样抗体具有双重功能(T 细胞受体和抗体),因此针对各种疾病进行了广泛的探索。在这项研究中,通过对人源抗体文库进行生物淘选,成功地产生了与主要组织相容性复合体 (MHC) HLA-A*02 呈递的结核分枝杆菌热休克蛋白 (HSP) 16kDa 抗原结合的 TCR 样结构域抗体 (A2/Ab)。生成的抗体 (A2/Ab) 对靶标表现出强大的功能和结合能力,确保了本研究的结果有利于未来潜伏性结核病诊断和免疫治疗的发展。

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