Changing T cell specificity by retroviral T cell receptor display.

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.

authors

Kessels HW,van Den Boom MD,Spits H,Hooijberg E,Schumacher TN

doi

10.1073/pnas.97.26.14578

keywords:

subject

Has Abstract

pub_date

2000-12-19 00:00:00

pages

14578-83

issue

26

eissn

0027-8424

issn

1091-6490

pii

97/26/14578

journal_volume

97

pub_type

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