Nonpeptide ligands for human γδ T cells

Yoshimasa Tanaka, Shigetoshi Sano, Edward Nieves, Gennaro De Libero, Domenico Rosa, Robert L. Modlin, Michael B. Brenner, Barry R. Bloom, Craig T. Morita

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341 Scopus citations


γδ 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 γδ T cells. Synthetic alkyl phosphates, particularly monoethyl phosphate (MEP), selectively activated γδ T cells and stimulated their proliferation in vitro. All γδ T cells stimulated by MEP expressed Vγ2/Vδ2 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 nonpeptide ligands is unprecedented among T cells. We suggest that MEP mimics small natural ligands capable of expanding one subset of γδ T cells and that this recognition of nonpeptide antigens may play an important role in human immunity to pathogens.

Original languageEnglish (US)
Pages (from-to)8175-8179
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
StatePublished - Aug 16 1994

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    Tanaka, Y., Sano, S., Nieves, E., De Libero, G., Rosa, D., Modlin, R. L., Brenner, M. B., Bloom, B. R., & Morita, C. T. (1994). Nonpeptide ligands for human γδ T cells. Proceedings of the National Academy of Sciences of the United States of America, 91(17), 8175-8179.