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T Cells by Nonpeptide Antigens1
Department of Immunology and Cell Biology, Graduate School of Biostudies, and Graduate School of Medicine, Kyoto University, Kyoto, Japan
Human V
2/V
2+ T cells respond to low
molecular-mass nonpeptide Ags in a TCR-dependent manner.
Although requirements of Ag presentation have remained controversial,
we have indicated that specific responses of the primary 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
T cells, inducing specific proliferation and IFN- production.
TCR dependency of the response to Ag-pulsed tumor cells was
confirmed by using a Jurkat line transfected with a V2/V2
TCR. Furthermore, 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 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 T cells but also may provide
a novel strategic clue for immunotherapy of human
malignancy.
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