Nonpeptide ligands for human gamma delta T cells.
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.
Tanaka
Y
Y
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461.
Sano
S
S
Nieves
E
E
De Libero
G
G
Rosa
D
D
Modlin
R L
RL
Brenner
M B
MB
Bloom
B R
BR
Morita
C T
CT
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*
D000906:Antibodies; D000942:Antigens, Bacterial; D008024:Ligands; D010755:Organophosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta; C088826:monoethyl phosphate