title: Contribution of Complementarity-Determining Region 3 of the T-Cell Receptor Vδ2 Chain to the Recognition of Aminobisphosphonates by Human γδ T-Cells.
abstract: Human gammadelta T-lymphocytes expressing Vgamma2Vdelta2 T-cell receptors (TCRs) can be stimulated by aminobisphosphonates and can kill certain tumor cells. Although germline-encoded lysine residues on the Jgamma1.2 segment have been demonstrated to be essential for the recognition of nonpeptide antigens by human gammadelta T-cells, the role of the junctional sequences of the TCR delta chain in the recognition of aminobisphosphonates by Vgamma2Vdelta2+ T-cells remains unknown. We examined the structure of complementarity-determining region 3 (CDR3) of Vdelta2 chains expressed by aminobisphosphonate-stimulated human gammadelta T-cells. CDR3 size-spectratyping analysis of Vdelta2 chains revealed that risedronate did not induce a CDR3 size distribution pattern of Vdelta2 cells that was distinct from that of Vdelta2 cells cultured without risedronate. The clonality of risedronate-expanded Vdelta2 T-cells was also determined by sequencing analysis, with the result that no particular consensus sequences were observed. However, most Vdelta2 T-cells freshly isolated from peripheral blood carried a distinctive junctional motif consisting of a hydrophobic amino acid residue (valine, leucine, or isoleucine [Val/Leu/Ile]) at conserved position 97, and this feature was not altered by risedronate stimulation. A significant proportion of Vdelta1 T-cells from the same individual had Leu at position 97, but Vdelta1 T-cells did not expand in response to risedronate. Moreover, Vdelta2 T-cells from the nonresponder against risedronate also carried a Val/Leu/Ile amino acid residue at position 97. These results suggest that the presence of a hydrophobic amino acid residue at position 97 in CDR3 of the TCR delta chain is not sufficient to account for the recognition of aminobisphosphonate by human gammadelta T-cells.
authors.affiliation: Department of Internal Medicine III, Akita University School of Medicine, Akita, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Nishimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirokawa
authors.forename: Naohito
authors.initials: N
authors.lastname: Fujishima
authors.forename: Masumi
authors.initials: M
authors.lastname: Fujishima
authors.forename: Ikuo
authors.initials: I
authors.lastname: Miura
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Sawada
mesh_terms: D000595:Amino Acid Sequence; D021542:Amino Acids, Neutral; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000032:analysis*; D004164:Diphosphonates / Q000276:immunology*; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008213:Lymphocyte Activation / Q000187:drug effects; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry* / Q000276:immunology*; D000068296:Risedronic Acid; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D021542:Amino Acids, Neutral; D022801:Complementarity Determining Regions; D004164:Diphosphonates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000068296:Risedronic Acid; D012968:Etidronic Acid