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Article Open Access

γδTCR immunoglobulin constant region domain exchange in human αβTCRs improves TCR pairing without altering TCR gene-modified T cell function

  • Authors:
    • Changli Tao
    • Hongwei Shao
    • Wenfeng Zhang
    • Huaben Bo
    • Fenglin Wu
    • Han Shen
    • Shulin Huang
  • View Affiliations / Copyright

    Affiliations: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong 510006, P.R. China
    Copyright: © Tao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1555-1564
    |
    Published online on: February 15, 2017
       https://doi.org/10.3892/mmr.2017.6206
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Abstract

The adoptive genetic transfer of T cell receptors (TCRs) has been shown to be overall feasible and offer clinical potential as a treatment for different types of cancer. However, this promising clinical approach is limited by the serious potential consequence that exogenous TCR mispairing with endogenous TCR chains may lead to the risk of self-reactivity. In the present study, domain‑exchange and three‑dimensional modeling strategies were used to create a set of chimeric TCR variants, which were used to exchange the partial or complete constant region of αβTCR with corresponding γδTCR domains. The expression, assembly and function of the chimeric TCR variants were examined in Jurkat T cells and peripheral mononuclear blood cells (PBMCs). Genetically‑encoded chimeras were fused with a pair of fluorescent proteins (ECFP/EYFP) to monitor expression and the pairing between chimeric TCRα chains and TCRβ chains. The fluorescence energy transfer based on confocal laser scanning microscopy showed that the introduction of γδTCR constant sequences into the αβTCR did not result in a global reduction of mispairing with endogenous TCR. However, the TCR harboring the immunoglobulin‑like domain of the γδTCR constant region (i.e., TCR∆IgC), showed a higher expression and preferential pairing, compared with wild‑type (wt)TCR. The function analysis showed that TCR∆IgC exhibited the same levels of interferon-γ production and cytotoxic activity, compared with wtTCR. Furthermore, these modified TCR-transduced T cells retained the classic human leukocyte antigen restriction of the original TCR. The other two chimeric TCRs, had either exchange of the cp+tm+ic domain or exchange of the whole C domain (Fig. 1). Ultimately, exchange of these domains demonstrated defective function in the transduced T cells. Taken together, these findings may provide further understanding of the γδTCR constant domain with implications for the improvement of TCR gene transfer therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Tao C, Shao H, Zhang W, Bo H, Wu F, Shen H and Huang S: γδTCR immunoglobulin constant region domain exchange in human αβTCRs improves TCR pairing without altering TCR gene-modified T cell function. Mol Med Rep 15: 1555-1564, 2017.
APA
Tao, C., Shao, H., Zhang, W., Bo, H., Wu, F., Shen, H., & Huang, S. (2017). γδTCR immunoglobulin constant region domain exchange in human αβTCRs improves TCR pairing without altering TCR gene-modified T cell function. Molecular Medicine Reports, 15, 1555-1564. https://doi.org/10.3892/mmr.2017.6206
MLA
Tao, C., Shao, H., Zhang, W., Bo, H., Wu, F., Shen, H., Huang, S."γδTCR immunoglobulin constant region domain exchange in human αβTCRs improves TCR pairing without altering TCR gene-modified T cell function". Molecular Medicine Reports 15.4 (2017): 1555-1564.
Chicago
Tao, C., Shao, H., Zhang, W., Bo, H., Wu, F., Shen, H., Huang, S."γδTCR immunoglobulin constant region domain exchange in human αβTCRs improves TCR pairing without altering TCR gene-modified T cell function". Molecular Medicine Reports 15, no. 4 (2017): 1555-1564. https://doi.org/10.3892/mmr.2017.6206
Copy and paste a formatted citation
x
Spandidos Publications style
Tao C, Shao H, Zhang W, Bo H, Wu F, Shen H and Huang S: γδTCR immunoglobulin constant region domain exchange in human αβTCRs improves TCR pairing without altering TCR gene-modified T cell function. Mol Med Rep 15: 1555-1564, 2017.
APA
Tao, C., Shao, H., Zhang, W., Bo, H., Wu, F., Shen, H., & Huang, S. (2017). γδTCR immunoglobulin constant region domain exchange in human αβTCRs improves TCR pairing without altering TCR gene-modified T cell function. Molecular Medicine Reports, 15, 1555-1564. https://doi.org/10.3892/mmr.2017.6206
MLA
Tao, C., Shao, H., Zhang, W., Bo, H., Wu, F., Shen, H., Huang, S."γδTCR immunoglobulin constant region domain exchange in human αβTCRs improves TCR pairing without altering TCR gene-modified T cell function". Molecular Medicine Reports 15.4 (2017): 1555-1564.
Chicago
Tao, C., Shao, H., Zhang, W., Bo, H., Wu, F., Shen, H., Huang, S."γδTCR immunoglobulin constant region domain exchange in human αβTCRs improves TCR pairing without altering TCR gene-modified T cell function". Molecular Medicine Reports 15, no. 4 (2017): 1555-1564. https://doi.org/10.3892/mmr.2017.6206
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