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Related Experiment Videos

CD1d-restricted T cell activation by nonlipidic small molecules.

Ildiko Van Rhijn1, David C Young, Jin Seon Im

  • 1Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, 1 Jimmy Fund Way, Boston, MA 02115, USA.

Proceedings of the National Academy of Sciences of the United States of America
|September 3, 2004
PubMed
Summary

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Researchers identified novel non-invariant CD1d-restricted T cells in humans. These cells respond to a unique non-lipidic small molecule, revealing new insights into T cell activation and autoimmune disease.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • The CD1d-restricted T cell repertoire includes invariant natural killer T (iNKT) cells and other T cells with diverse T cell receptors (TCRs).
  • These diverse TCRs play roles in inflammation during autoimmune and infectious diseases.

Purpose of the Study:

  • To isolate and characterize human Valpha24(-) T cells activated by CD1d-presented antigens.
  • To determine the molecular structure of the activating antigen and elucidate the mechanism of T cell activation.

Main Methods:

  • Isolation of human Valpha24(-) T cells.
  • Mass spectrometry and Nuclear Magnetic Resonance (NMR) studies to identify compound structure.
  • Analysis of T cell activation signaling pathways.

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Main Results:

  • Identified human Valpha24(-) T cells activated by CD1d.
  • Determined the stimulatory compounds are phenyl pentamethyldihydrobenzofuran sulfonates, containing sulfur and aromatic hydrocarbon rings.
  • Demonstrated a specific Valpha2/Vbeta21 TCR mediates activation, sensitive to hydroxylation and methylation patterns of the antigen.

Conclusions:

  • Provided evidence for noninvariant CD1d-restricted T cells in humans.
  • Identified the complete molecular structure of a nonlipidic small molecule activating T cells via an alpha beta TCR.
  • Highlighted the specificity of TCR recognition for non-peptide, non-lipid antigens.