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研究一种针对热休克蛋白（HSP）16KDa/HLA-A2的T细胞受体（TCR）样单域抗体（sDAb）-人IgG1抗体对潜伏性结核的诊断和治疗潜力。

Investigating the Diagnostic and Therapeutic Potential of a T Cell Receptor (TCR)-like single Domain Antibody (sDAb)-Human IgG1 Antibody against Heat Shock Protein (HSP) 16KDa/HLA-A2 for Latent Tuberculosis.

作者信息

Liu Huaqiang, Dass Sylvia Annabel, Wong Matthew Tze Jian, Balakrishnan Venugopal, Nordin Fazlina, Tye Gee Jun

机构信息

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

Biogenes Technologies, Jalan Maklumat, University Putra Malaysia, Serdang 43400, Malaysia.

出版信息

Trop Med Infect Dis. 2024 Jun 26;9(7):139. doi: 10.3390/tropicalmed9070139.

DOI:10.3390/tropicalmed9070139
PMID:39058181
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11281560/
Abstract

Heat shock protein 16-kDa (HSP 16-kDa) is essential for the survival of () during the latent period; hence, a peptide-MHC presentation of HSP 16-kDa could be a potential diagnostic and therapeutic target for latent tuberculosis (LTB). This study aimed to generate a TCR-like single-domain antibody (sDAb)-human IgG1 antibody and subsequently investigate its diagnostic and therapeutic potential in LTB, utilizing a model cell presenting the target peptide. A previously generated TCR-like sDAB that can bind to HSP 16-kDa was first fused to a human IgG1 Fc-receptor via a linker. The fusion product, sDAb-IgG1, was expressed with HEK293-F and was subsequently purified. Its diagnostic potential was investigated via cell-based ELISA utilizing MCF-7 cells peptide-pulsed with HSP 16-kDa peptides. Investigation into the antibody-dependent cell-mediated cytotoxicity (ADCC) of MCF-7 cells was also conducted to investigate its therapeutic potential. Finally, TCR-like sDAb-IgG1 was successfully produced transiently with HEK-293F and was purified using protein A chromatography. The generated antibody was tested using cell-based ELISA, which demonstrated the effective binding of the TCR-like sDAb-IgG1 to the 16-kDa peptide-MHC on the cell surface. The ADCC assay also showed that the antibody effectively mediated the ADCC of MCF-7 cells with the help of 16-kDa peptide-MHC. This allows us to hypothesize the possible utility of the said antibody for both diagnostics and therapeutics of latent tuberculosis after more investigations with clinical samples.

摘要

热休克蛋白16 kDa（HSP 16 kDa）对于（）在潜伏期的存活至关重要；因此，HSP 16 kDa的肽-MHC呈递可能是潜伏性结核病（LTB）的潜在诊断和治疗靶点。本研究旨在生成一种TCR样单域抗体（sDAb）-人IgG1抗体，随后利用呈现靶肽的模型细胞研究其在LTB中的诊断和治疗潜力。首先，通过接头将先前生成的能够与HSP 16 kDa结合的TCR样sDAB与人IgG1 Fc受体融合。融合产物sDAb-IgG1在HEK293-F中表达，随后进行纯化。通过基于细胞的ELISA，利用用HSP 16 kDa肽脉冲处理的MCF-7细胞研究其诊断潜力。还对MCF-7细胞的抗体依赖性细胞介导的细胞毒性（ADCC）进行了研究，以探讨其治疗潜力。最后，TCR样sDAb-IgG1成功地在HEK-293F中瞬时产生，并使用蛋白A层析进行纯化。使用基于细胞的ELISA对产生的抗体进行测试，结果表明TCR样sDAb-IgG1与细胞表面的16 kDa肽-MHC有效结合。ADCC试验还表明，该抗体在16 kDa肽-MHC的帮助下有效地介导了MCF-7细胞的ADCC。这使我们能够假设，在对临床样本进行更多研究后，所述抗体在潜伏性结核病的诊断和治疗中可能具有实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c14/11281560/03fa3a4dc5fa/tropicalmed-09-00139-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c14/11281560/4ed13f039ed7/tropicalmed-09-00139-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c14/11281560/e16abb4a887d/tropicalmed-09-00139-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c14/11281560/69290491ef77/tropicalmed-09-00139-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c14/11281560/03fa3a4dc5fa/tropicalmed-09-00139-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c14/11281560/4ed13f039ed7/tropicalmed-09-00139-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c14/11281560/e16abb4a887d/tropicalmed-09-00139-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c14/11281560/69290491ef77/tropicalmed-09-00139-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c14/11281560/03fa3a4dc5fa/tropicalmed-09-00139-g004.jpg

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本文引用的文献

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Heat Shock Response and Heat Shock Proteins: Current Understanding and Future Opportunities in Human Diseases.热休克反应与热休克蛋白：对人类疾病的当前认识及未来机遇
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