Chemical synthesis and biological activity of bromohydrin pyrophosphate, a potent stimulator of human gamma delta T cells.
Small phosphorylated metabolites from mycobacteria stimulate human gammadelta T lymphocytes. Although such phosphoantigens could prove useful in the composition of vaccines involving gammadelta T cell-mediated immunity, their very low abundance in natural sources limits such applications. Here, we describe the chemical production, purification, and bioactivity of a phosphorylated bromohydrin (BrHPP) analogue that mimics the biological properties of natural phosphoantigens. This compound can be obtained in gram amounts, is easy to detect, and is of high stability in aqueous solutions. Whereas unspecific binding of BrHPP to a wide panel of cell surface receptors is not detected even at micromolar concentrations, nanomolar concentrations specifically trigger effector responses of human gammadelta T lymphocytes. Thus, BrHPP is a novel molecule enabling potent immunostimulation of human gammadelta T lymphocytes.
Espinosa
E
E
INSERM U395, CHU Purpan, BP3028, 31024 Toulouse, INSERM U463, Institut de Biologie, Quai Moncousu, 44035 Nantes, France.
Belmant
C
C
Pont
F
F
Luciani
B
B
Poupot
R
R
Romagné
F
F
Brailly
H
H
Bonneville
M
M
Fournié
J J
JJ
D000438:Alcohols / Q000138:chemical synthesis* / Q000494:pharmacology*; D011756:Diphosphates / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000438:Alcohols; D011756:Diphosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta; C429553:bromohydrin pyrophosphate; C023963:bromohydrins