Abstract
Human γδ T-lymphocytes expressing Vγ2Vδ2 T-cell receptors (TCRs) can be stimulated by aminobisphosphonates and can kill certain tumor cells. Although germline-encoded lysine residues on the Jγ1.2 segment have been demonstrated to be essential for the recognition of nonpeptide antigens by human γδ T-cells, the role of the junctional sequences of the TCR δ chain in the recognition of aminobisphosphonates by Vγ2Vδ2+T-cells remains unknown. We examined the structure of complementarity-determining region 3 (CDR3) of Vδ2 chains expressed by aminobisphosphonate-stimulated human γδ T-cells. CDR3 size-spectratyping analysis of Vδ2 chains revealed that risedronate did not induce a CDR3 size distribution pattern of Vδ2 cells that was distinct from that of Vδ2 cells cultured without risedronate. The clonality of risedronate-expanded Vδ2 T-cells was also determined by sequencing analysis, with the result that no particular consensus sequences were observed. However, most Vδ2 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 Vδ1 T-cells from the same individual had Leu at position 97, but Vδ1 T-cells did not expand in response to risedronate. Moreover, Vδ2 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 δ chain is not sufficient to account for the recognition of aminobisphosphonate by human γδ T-cells.
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Nishimura, H., Hirokawa, M., Fujishima, N. et al. Contribution of Complementarity-Determining Region 3 of the T-Cell Receptor Vδ2 Chain to the Recognition of Aminobisphosphonates by Human γδ T-Cells. Int J Hematol 79, 369–376 (2004). https://doi.org/10.1532/IJH97.03157
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DOI: https://doi.org/10.1532/IJH97.03157