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.
journal_name
Proc Natl Acad Sci U S Aauthors
Kessels HW,van Den Boom MD,Spits H,Hooijberg E,Schumacher TNdoi
10.1073/pnas.97.26.14578keywords:
subject
Has Abstractpub_date
2000-12-19 00:00:00pages
14578-83issue
26eissn
0027-8424issn
1091-6490pii
97/26/14578journal_volume
97pub_type
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