title: Involvement of CD166 in the activation of human gamma delta T cells by tumor cells sensitized with nonpeptide antigens.
abstract: We previously reported that human Vgamma2Vdelta2-gammadelta T cells were activated by many human tumor cell lines treated with pamidronate (PAM) in a gammadelta TCR-dependent manner. In the present study, we indicated that a synthetic pyrophosphomonoester Ag, 2-methy-3-butenyl-1-pyrophosphate, could directly "sensitize" the tumor cells to activate gammadelta T cells independently of the host metabolism, while the sensitizing effect of PAM was reported to be dependent on the pharmacological activity. Some exceptional tumor cells that failed to be sensitized by PAM were incapable of activating gammadelta T cells by the treatment with 2-methy-3-butenyl-1-pyrophosphate either, suggesting a requirement of host factor(s) for the effective gammadelta T cell activation in addition to the nonpeptide Ags. By screening mAbs against a large panel of tumor cell lines, we found that the expression of CD166 closely paralleled the capacity of activating gammadelta T cells upon PAM treatment. The transfection of a CD166-negative tumor cell line with CD166 cDNA caused a marked enhancement of the capacity to activate gammadelta T cells following PAM treatment. On the contrary, down-regulation of the CD166 expression in a CD166-bearing tumor cell line by short hairpin RNA resulted in a significant reduction of PAM-induced gammadelta T cell-stimulatory activity. gammadelta T cells expressed CD6, a receptor of CD166, and CD6 and CD166 were recruited together to the center of synapse between gammadelta T cells and PAM-treated tumor cells, colocalizing with gammadelta TCR/CD3. The results suggested that the engagement of CD6 with CD166 on tumor cells played an important role in the gammadelta T cell activation by the tumor cells loaded with nonpeptide Ags either endogenously or exogenously.
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kato
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Mikihito
authors.initials: M
authors.lastname: Hayashi
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Minato
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000378:metabolism; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D002999:Clone Cells; D004164:Diphosphonates / Q000276:immunology; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D000077268:Pamidronate; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015816:Cell Adhesion Molecules, Neuronal; D004164:Diphosphonates; D005326:Fetal Proteins; D000077268:Pamidronate; D016692:Receptors, Antigen, T-Cell, gamma-delta; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C062279:CD6 antigen