Various microorganisms including mycobacteria, other bacteria, and par
asites such as Plasmodium falciparum are known to activate human gamma
delta T-cells in vitro. In this study, we demonstrate that heat-treat
ed (but not untreated) mistletoe extracts similarly stimulate human ga
mma delta T-cells during in vitro culture. The responding T-cells expr
ess the variable T-cell receptor elements V gamma 9 and V delta 2. The
gamma delta-stimulating activity of heat-treated mistletoe extracts i
s sensitive to treatment with alkaline phosphatase but not with protei
nase K, indicating that the ligands are non-proteinaceous phosphate-co
ntaining compounds. Mistletoe-derived ligands share these features wit
h the previously defined mycobacteria-derived ligands for gamma delta
T-cells.