CD1d-restricted T cell activation by nonlipidic small molecules

Ildiko Van Rhijn, David C. Young, Jin Seon Im, Steven B. Levery, Petr A. Illarionov, Gurdyal S. Besra, Steven A. Porcelli, Jenny Gumperz, Tan Yun Cheng, D. Branch Moody

Research output: Contribution to journalArticle

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Abstract

In addition to NK T cells expressing invariant Vα14 or Vα24 T cell receptors (TCRs), the CD1d-restricted T cell repertoire is comprised of T cells with diverse TCRs that mediate inflammation during autoimmune and infectious disease. Here we describe the isolation of human Vα24 - T cells that are activated by antigen and CD1d. Mass spectrometric and NMR studies revealed that the stimulatory compounds were neither peptidic nor lipidic but instead were composed of sulfur and aromatic hydrocarbon rings, corresponding to the general structure of phenyl pentamethyldihydrobenzofuran sulfonates. Studies of the molecular mechanism of T cell activation showed that a clonotypic Vα2/Vβ21 TCR transmitted activating signals, which were highly specific for hydroxylation and methylation patterns at the terminal structures of stimulatory compounds. These studies provide evidence for noninvariant CD1d-restricted T cells in humans and identify the complete molecular structure of a nonlipidic small molecule that activates T cells through an αβ TCR.

Original languageEnglish (US)
Pages (from-to)13578-13583
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number37
DOIs
StatePublished - Sep 14 2004

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T-Lymphocytes
T-Cell Antigen Receptor
CD1d Antigen
Aromatic Hydrocarbons
Hydroxylation
Molecular Structure
Sulfur
Natural Killer Cells
Methylation
Autoimmune Diseases
Communicable Diseases
Inflammation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Van Rhijn, I., Young, D. C., Im, J. S., Levery, S. B., Illarionov, P. A., Besra, G. S., ... Moody, D. B. (2004). CD1d-restricted T cell activation by nonlipidic small molecules. Proceedings of the National Academy of Sciences of the United States of America, 101(37), 13578-13583. https://doi.org/10.1073/pnas.0402838101

CD1d-restricted T cell activation by nonlipidic small molecules. / Van Rhijn, Ildiko; Young, David C.; Im, Jin Seon; Levery, Steven B.; Illarionov, Petr A.; Besra, Gurdyal S.; Porcelli, Steven A.; Gumperz, Jenny; Cheng, Tan Yun; Moody, D. Branch.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 37, 14.09.2004, p. 13578-13583.

Research output: Contribution to journalArticle

Van Rhijn, I, Young, DC, Im, JS, Levery, SB, Illarionov, PA, Besra, GS, Porcelli, SA, Gumperz, J, Cheng, TY & Moody, DB 2004, 'CD1d-restricted T cell activation by nonlipidic small molecules', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 37, pp. 13578-13583. https://doi.org/10.1073/pnas.0402838101
Van Rhijn, Ildiko ; Young, David C. ; Im, Jin Seon ; Levery, Steven B. ; Illarionov, Petr A. ; Besra, Gurdyal S. ; Porcelli, Steven A. ; Gumperz, Jenny ; Cheng, Tan Yun ; Moody, D. Branch. / CD1d-restricted T cell activation by nonlipidic small molecules. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 37. pp. 13578-13583.
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