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Nonpeptide ligands for human gamma delta T cells
Journal article   Open access   Peer reviewed

Nonpeptide ligands for human gamma delta T cells

Y Tanaka, S Sano, E Nieves, G De Libero, D Rosa, R L Modlin, M B Brenner, B R Bloom and C T Morita
Proceedings of the National Academy of Sciences - PNAS, Vol.91(17), pp.8175-8179
08/16/1994
DOI: 10.1073/pnas.91.17.8175
PMCID: PMC44568
PMID: 8058775
url
https://doi.org/10.1073/pnas.91.17.8175View
Published (Version of record) Open Access

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.
Organophosphates - metabolism Lymphocyte Activation Humans Mycobacterium tuberculosis - immunology Antigens, Bacterial - pharmacology Receptors, Antigen, T-Cell, gamma-delta - immunology Receptors, Antigen, T-Cell, gamma-delta - drug effects Antibodies - pharmacology Organophosphates - pharmacology Synovial Fluid - immunology Receptors, Antigen, T-Cell, gamma-delta - physiology Flow Cytometry T-Lymphocytes - drug effects Ligands T-Lymphocytes - immunology Clone Cells Arthritis, Rheumatoid - immunology Cytotoxicity, Immunologic

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