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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere54697
JournalJournal of Visualized Experiments
Volume2016
Issue number116
DOIs
Publication statusPublished - 2016 Oct 25
Externally publishedYes

Keywords

  • Antigen-presenting cell
  • Antigen-specificity
  • Cloning
  • Hemichain
  • Human
  • Immunology
  • Issue 116
  • Retroviral transduction
  • T cell
  • T cell receptor

ASJC Scopus subject areas

  • General Neuroscience
  • General Chemical Engineering
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology

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