Targeting of Tumor Cells for Human γδ T Cells by Nonpeptide Antigens

• Published in: The Journal of immunology (1950) 2001-11, Vol.167 (9), p.5092-5098
• Main Authors: Kato, Yu, Tanaka, Yoshimasa, Miyagawa, Fumi, Yamashita, Seiji, Minato, Nagahiro
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.9.5092

Human Vγ2/Vδ2+ γδ T cells respond to low molecular-mass nonpeptide Ags in a γδ TCR-dependent manner. Although requirements of Ag presentation have remained controversial, we have indicated that specific responses of the primary γδ T cells to pamidronate were dependent on monocytic adherent cells for Ag presentation. Here, we show that human tumor cells can efficiently present aminobisphosphonate and pyrophosphomonoester compounds to γδ T cells, inducing specific proliferation and IFN-γ production. γδ TCR dependency of the response to Ag-pulsed tumor cells was confirmed by using a Jurkat line transfected with a Vγ2/Vδ2 γδ TCR. Furthermore, γδ T cells exhibited markedly enhanced cytotoxicity against the Ag-pulsed tumor cells as compared with untreated tumor cells. Survey of a number of human tumor cell lines of different origins revealed that the majority of them became susceptible for γδ T cell-mediated cytotoxicity following the Ag pulsing except for breast cancer lines so far examined, while normal PHA blast cells remained resistant. The results not only imply a unique mode of nonpeptide Ag recognition by human γδ T cells but also may provide a novel strategic clue for immunotherapy of human malignancy.