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

Research output: Contribution to journalArticle

333 Citations (Scopus)

Abstract

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
Volume91
Issue number17
DOIs
StatePublished - Aug 16 1994

Fingerprint

Ligands
T-Lymphocytes
Antigens
Phosphates
Vasopressin Receptors
T-Lymphocyte Subsets
Mycobacterium
T-Cell Antigen Receptor
Immunity
Peptide Hydrolases
monoethyl phosphate
Population

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Nonpeptide ligands for human γδ T cells. / Tanaka, Yoshimasa; Sano, Shigetoshi; Nieves, Edward; De Libero, Gennaro; Rosa, Domenico; Modlin, Robert L.; Brenner, Michael B.; Bloom, Barry R.; Morita, Craig T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 17, 16.08.1994, p. 8175-8179.

Research output: Contribution to journalArticle

Tanaka, Y, Sano, S, Nieves, E, De Libero, G, Rosa, D, Modlin, RL, Brenner, MB, Bloom, BR & Morita, CT 1994, 'Nonpeptide ligands for human γδ T cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 17, pp. 8175-8179. https://doi.org/10.1073/pnas.91.17.8175
Tanaka, Yoshimasa ; Sano, Shigetoshi ; Nieves, Edward ; De Libero, Gennaro ; Rosa, Domenico ; Modlin, Robert L. ; Brenner, Michael B. ; Bloom, Barry R. ; Morita, Craig T. / Nonpeptide ligands for human γδ T cells. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 17. pp. 8175-8179.
@article{954fa056af634ea68a7b66ccb6ab4a55,
title = "Nonpeptide ligands for human γδ T cells",
abstract = "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.",
author = "Yoshimasa Tanaka and Shigetoshi Sano and Edward Nieves and {De Libero}, Gennaro and Domenico Rosa and Modlin, {Robert L.} and Brenner, {Michael B.} and Bloom, {Barry R.} and Morita, {Craig T.}",
year = "1994",
month = "8",
day = "16",
doi = "10.1073/pnas.91.17.8175",
language = "English (US)",
volume = "91",
pages = "8175--8179",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "17",

}

TY - JOUR

T1 - Nonpeptide ligands for human γδ T cells

AU - Tanaka, Yoshimasa

AU - Sano, Shigetoshi

AU - Nieves, Edward

AU - De Libero, Gennaro

AU - Rosa, Domenico

AU - Modlin, Robert L.

AU - Brenner, Michael B.

AU - Bloom, Barry R.

AU - Morita, Craig T.

PY - 1994/8/16

Y1 - 1994/8/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0027932245&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027932245&partnerID=8YFLogxK

U2 - 10.1073/pnas.91.17.8175

DO - 10.1073/pnas.91.17.8175

M3 - Article

VL - 91

SP - 8175

EP - 8179

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 17

ER -