T cell receptor engineering

Jennifer D. Stone, Adam S. Chervin, David H. Aggen, David M. Kranz

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

T lymphocytes express on their surface a heterodimeric αβ receptor, called the T cell receptor (TCR), which recognizes foreign antigens. Unlike antibodies, the recognition requires both an antigenic peptide epitope and a protein encoded by the major histocompatibility complex (MHC). In contrast to conventional antibody-directed target antigens, antigens recognized by the TCR can include the entire array of potential intracellular proteins, which are processed and delivered to the cell surface as a peptide/MHC complex. In the past 10 years, there have been significant efforts to engineer TCRs in various formats, which would allow improved recognition and destruction of virus-infected cells or cancer. The proposed therapeutic approaches involve either the use of engineered, high-affinity TCRs in soluble forms, analogous to antibody-directed therapies, or the use of engineered TCRs whose genes are reintroduced into autologous T cells and transferred back into patients (T cell adoptive therapies). This chapter describes three methods associated with the engineering of TCRs for these therapeutic purposes: (1) use of a yeast display system to engineer higher affinity single-chain VαVβ TCRs, called scTv; (2) use of a T cell display system to engineer higher affinity full-length TCRs; and (3) expression, purification, and characterization of soluble TCRs in an Escherichia coli system.

Original languageEnglish (US)
Title of host publicationMethods in Enzymology
PublisherAcademic Press Inc.
Pages189-222
Number of pages34
DOIs
StatePublished - 2012

Publication series

NameMethods in Enzymology
Volume503
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Keywords

  • Complementarity-determining regions
  • Fluorescence-activated cell sorting
  • Keywords
  • Major histocompatibility complex
  • Protein engineering
  • Splicing by overlap extension
  • T cell display
  • T cell receptor
  • Yeast display

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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  • Cite this

    Stone, J. D., Chervin, A. S., Aggen, D. H., & Kranz, D. M. (2012). T cell receptor engineering. In Methods in Enzymology (pp. 189-222). (Methods in Enzymology; Vol. 503). Academic Press Inc.. https://doi.org/10.1016/B978-0-12-396962-0.00008-2