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Requirement of Species-Specific Interactions for the Activation of Human T Cells by Pamidronate¹

Yu Kato^*, Yoshimasa Tanaka^*,, Hidenori Tanaka, Seiji Yamashita^* and Nagahiro Minato^2,*,

^* Department of Immunology and Cell Biology, Graduate Schools of Biostudies and Medicine, Kyoto University, Kyoto, Japan; and PRESTO, JST, Kyoto, Japan

Human T cells bearing V2V2-TCR recognize various kinds of small nonpeptide Ags, and activation of them by a nitrogen-containing bisphosphonate Ag, pamidronate, requires Ag presentation by cells other than T cells, including many human tumor cells. Present results demonstrated that tumor cell lines of nonhuman origins pulsed with pamidronate failed to activate human T cells without exception, whereas most if not all human tumor cell lines could do so. T cells formed stable conjugates with pamidronate-pulsed human tumor cells and both conjugate formation and T cell activation were inhibited significantly by anti-LFA-1 mAb, suggesting the requirement of LFA-1-mediated interaction with APC for efficient T cell activation. Consistently, ICAM-1^low tumor cell lines pulsed with pamidronate induced no or only weak activation of T cells, whereas similarly treated ICAM-1^high cell lines could activate them. One of the two ICAM-1^low tumor cell lines pulsed with pamidronate induced strong T cell activation after ICAM-1 gene transfer. However, another ICAM-1^low human cell line as well as murine tumor cell lines pulsed with pamidronate remained totally defective in T cell activation even after expression of human ICAM-1. These results suggested that activation of human T cells by nonpeptide Ags required species-specific interactions in addition to LFA-1/ICAM-1-mediated cell adhesion with APC.

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