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The Journal of Immunology, 2000, 165: 528-532.
Copyright © 2000 by The American Association of Immunologists

Functional Reconstitution of Class II MHC-Restricted T Cell Immunity Mediated by Retroviral Transfer of the {alpha}ß TCR Complex1

Keishi Fujio*,{dagger}, Yoshikata Misaki{dagger}, Keigo Setoguchi{dagger}, Sumiyo Morita*, Kimito Kawahata{dagger}, Ikunoshin Kato{ddagger}, Tetsuya Nosaka*, Kazuhiko Yamamoto{dagger} and Toshio Kitamura2,*

* Department of Hematopoietic Factors, Institute of Medical Science, University of Tokyo, Tokyo, Japan; {dagger} Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; and {ddagger} Biotechnology Research Laboratories, Takara Shuzo, Shiga, Japan

Transfer of the {alpha}ß TCR genes into T lymphocytes will provide a means to enhance Ag-specific immunity by increasing the frequency of tumor- or pathogen-specific T lymphocytes. We generated an efficient {alpha}ß TCR gene transfer system using two independent monocistronic retrovirus vectors harboring either of the class II MHC-restricted {alpha} or ß TCR genes specific for chicken OVA. The system enabled us to express the clonotypic TCR in 44% of the CD4+ T cells. The transduced cells showed a remarkable response to OVA323–339 peptide in the in vitro culture system, and the response to the Ag was comparable with those of the T lymphocytes derived from transgenic mice harboring OVA-specific TCR. Adoptive transfer of the TCR-transduced cells in mice induced the Ag-specific delayed-type hypersensitivity in response to OVA323–339 challenge. These results indicate that {alpha}ß TCR gene transfer into peripheral T lymphocytes can reconstitute Ag-specific immunity. We here propose that this method provides a basis for a new approach to manipulation of immune reactions and immunotherapy.




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