Changing T cell specificity by retroviral T cell receptor display.

H W Kessels, M D van Den Boom, H Spits, E Hooijberg, T N Schumacher

Department of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Proceedings of the National Academy of Sciences of the United States of America 2000 Dec 19

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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.

Citation

H W Kessels, M D van Den Boom, H Spits, E Hooijberg, T N Schumacher. Changing T cell specificity by retroviral T cell receptor display. Proceedings of the National Academy of Sciences of the United States of America. 2000 Dec 19;97(26):14578-83