A novel nucleotide-containing antigen for human blood gamma delta T lymphocytes

2020-03-30 06:39:34

cells delta antigens gamma nucleotide

责任者: Poquet, Y;Constant, P;Halary, F;Peyrat, MA;Gilleron, M;Davodeau, F;Bonneville, M;Fournie, JJ 单位: CHU PURPAN,INSERM U395,F-31024 TOULOUSE,FRANCE.;IPBS,CNRS,TOULOUSE,FRANCE.;INST BIOL,INSERM U211,NANTES,FRANCE. 来源出处: EUROPEAN JOURNAL OF IMMUNOLOGY, v 26, OCT 1996, p 2344- 2349 摘要: The stimulation of human gamma delta T cells by mycobacteria occurs through recognition of our distinct nonpeptide phosphorylated antigens termed TUBag1-4. Among these latter, TUBag4 has already been biochemically characterized as a gamma-X derivative of 5-deosythymidine triphosphate (Constant, P., Davodeau, F, Peyrat, M. A.: Poquet, Y., Puzo, G,, Bonneville, M. and Fournie, J.-J., Science 1991. 264: 267). However, despite chemical synthesis of weakly stimulatory nucleotide-containing analogs, these mycobacterial compounds remained the sole nucleotide-containing antigens actually isolated from natural sources, Here, we present the complete isolation of the TUBag3 antigen from Mycobacterium fortuitum and demonstrate that this nonpeptide molecule contains a 5-UTP nucleotide moiety. On selected V gamma 9/V delta 2 clones, T cell responses can be triggered with nanomolar concentrations of TUBag3, Like crude mycobacterial extracts, this purified nucleotide conjugate elicits a strong polyclonal response of gamma delta PBL from healthy donors, Furthermore, we present evidence that this compound is distinct from the recently synthesized gamma-isopentenyl 5-UTP, a nucleotide conjugate of isopentenyl pyrophosphate that was found to be stimulatory for human gamma delta T cells (Tanaka, Y., Morita, C. T., Tanaka, Y., Nieves, E., Brenner, M. B, and Bloom, B. R., Nature 1995. 375: 155). Since it appears that both mycobacterial nucleotide antigens are molecules structurally related to peculiar precursors of nucleic acid synthesis, we propose that TUBag-reactive T cells might be specifically devoted to surveillance of proliferating cells. 关键词: gamma delta T lymphocytes; mycobacteria; antigens; activation; NONPEPTIDIC MYCOBACTERIAL LIGANDS; CELLS; RESPONSES; FRACTION; PROTEIN