Changing T cell specificity by retroviral T cell receptor display

Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14578-83. doi: 10.1073/pnas.97.26.14578.

Abstract

The diversity of the T cell receptor (TCR) repertoire is limited, because of the processes of positive and negative T cell selection. To obtain T cells with specificities beyond the immune system's capacity, we have developed a strategy for retroviral TCR display. In this approach, a library of T cell variants is generated in vitro and introduced into a TCR-negative murine T cell line by retroviral transfer. We document the value of TCR display by the creation of a library of an influenza A-specific TCR and the subsequent in vitro selection of TCRs that either recognize the parental influenza epitope or that have acquired a specificity for a different influenza A strain. The resulting in vitro selected TCRs induce efficient T cell activation after ligand recognition and are of equal or higher potency than the in vivo generated parent receptor. TCR display should prove a useful strategy for the generation of high-affinity tumor-specific TCRs for gene transfer purposes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Genetic Vectors
  • H-2 Antigens / immunology
  • Histocompatibility Antigen H-2D
  • Humans
  • Mice
  • Nucleoproteins / immunology
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Retroviridae
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Core Proteins / immunology

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Nucleoproteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • Viral Core Proteins
  • nucleoprotein (366-374), influenza virus