title: Nonpeptide ligands for human gamma delta T cells.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Sano
authors.forename: E
authors.initials: E
authors.lastname: Nieves
authors.forename: G
authors.initials: G
authors.lastname: De Libero
authors.forename: D
authors.initials: D
authors.lastname: Rosa
authors.forename: R L
authors.initials: RL
authors.lastname: Modlin
authors.forename: M B
authors.initials: MB
authors.lastname: Brenner
authors.forename: B R
authors.initials: BR
authors.lastname: Bloom
authors.forename: C T
authors.initials: CT
authors.lastname: Morita
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010755:Organophosphates / Q000378:metabolism / Q000494:pharmacology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013582:Synovial Fluid / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000906:Antibodies; D000942:Antigens, Bacterial; D008024:Ligands; D010755:Organophosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta; C088826:monoethyl phosphate