Nonpeptide ligands for human gamma delta T cells.

Y Tanaka, S Sano, E Nieves… - Proceedings of the …, 1994 - National Acad Sciences
Y Tanaka, S Sano, E Nieves, G De Libero, D Rosa, RL Modlin, MB Brenner, BR Bloom…
Proceedings of the National Academy of Sciences, 1994National Acad Sciences
gamma delta T cells respond to a variety of microbial pathogens and transformed cells. Their
limited receptor repertoire and activation by mycobacterial antigens resistant to proteases
suggest that they may recognize nonpeptide antigens. We have tested a variety of
nonpeptide molecules for stimulation of human gamma delta T cells. Synthetic alkyl
phosphates, particularly monoethyl phosphate (MEP), selectively activated gamma delta T
cells and stimulated their proliferation in vitro. All gamma delta T cells stimulated by MEP …
gamma delta T cells respond to a variety of microbial pathogens and transformed cells. Their limited receptor repertoire and activation by mycobacterial antigens resistant to proteases suggest that they may recognize nonpeptide antigens. We have tested a variety of nonpeptide molecules for stimulation of human gamma delta T cells. Synthetic alkyl phosphates, particularly monoethyl phosphate (MEP), selectively activated gamma delta T cells and stimulated their proliferation in vitro. All gamma delta T cells stimulated by MEP expressed V gamma 2/V delta 2 receptors. The purified natural ligand of mycobacteria is chemically similar to, though distinct from, MEP and contains a phosphate residue that is critical for biological activity. Recognition and expansion of a specific T-cell receptor-bearing population to non-peptide ligands is unprecedented among T cells. We suggest that MEP mimics small natural ligands capable of expanding one subset of gamma delta T cells and that this recognition of nonpeptide antigens may play an important role in human immunity to pathogens.
National Acad Sciences