Generating de novo antigen-specific human T cell receptors by retroviral transduction of centric hemichain

Tingxi Guo, Toshiki Ochi, Munehide Nakatsugawa, Yuki Kagoya, Mark Anczurowski, Chung Hsi Wang, Muhammed A. Rahman, Kayoko Saso, Marcus O. Butler, Naoto Hirano

研究成果: Article査読

3 被引用数 (Scopus)

抄録

T cell receptors (TCRs) are used clinically to direct the specificity of T cells to target tumors as a promising modality of immunotherapy. Therefore, cloning TCRs specific for various tumor-associated antigens has been the goal of many studies. To elicit an effective T cell response, the TCR must recognize the target antigen with optimal affinity. However, cloning such TCRs has been a challenge and many available TCRs possess sub-optimal affinity for the cognate antigen. In this protocol, we describe a method of cloning de novo high affinity antigen-specific TCRs using existing TCRs by exploiting hemichain centricity. It is known that for some TCRs, each TCRα or TCRβ hemichain do not contribute equally to antigen recognition, and the dominant hemichain is referred to as the centric hemichain. We have shown that by pairing the centric hemichain with counter-chains differing from the original counter-chain, we are able to maintain the antigen specificity, while modulating its interaction strength for the cognate antigen. Thus, the therapeutic potential of a given TCR can be improved by optimizing the pairing between the centric and counter hemichains.

本文言語English
論文番号e54697
ジャーナルJournal of Visualized Experiments
2016
116
DOI
出版ステータスPublished - 2016 10月 25
外部発表はい

ASJC Scopus subject areas

  • 神経科学一般
  • 化学工学一般
  • 生化学、遺伝学、分子生物学一般
  • 免疫学および微生物学一般

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