NONPEPTIDE LIGANDS FOR HUMAN GAMMA-DELTA T-CELLS

gamma delta T cells respond to a variety of microbial pathogens and tr ansformed cells. Their limited receptor repertoire and activation by m ycobacterial antigens resistant to proteases suggest that they may rec ognize nonpeptide antigens. We have tested a variety of nonpeptide mol ecules for stimulation of human gamma delta T cells. Synthetic alkyl p hosphates, particularly monoethyl phosphate (MEP), selectively activat ed gamma delta T cells and stimulated their proliferation in vitro. Al l gamma delta T cells stimulated by MEP expressed V gamma 2/V delta 2 receptors. The purified natural ligand of mycobacteria is chemically s imilar 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 nonpeptide ligands i s unprecedented among T cells. We suggest that MEP mimics small natura l ligands capable of expanding one subset of gamma delta T cells and t hat this recognition of nonpeptide antigens may play an important role in human immunity to pathogens.