Open AccessCD1d-restricted T cell activation by nonlipidic small molecules
Author(s) -
Ildiko Van Rhijn,
David C. Young,
Jin S. Im,
Steven B. Levery,
Petr A. Illarionov,
Gurdyal S. Besra,
Steven A. Porcelli,
Jenny E. Gumperz,
Tan Yun Cheng,
D. Branch Moody
Publication year - 2004
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0402838101
Subject(s) - cd1d , t cell receptor , t cell , microbiology and biotechnology , natural killer t cell , biology , antigen , chemistry , antigen presenting cell , receptor , immune system , biochemistry , immunology
In addition to NK T cells expressing invariant Valpha14 or Valpha24 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 Valpha24(-) 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 Valpha2/Vbeta21 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 alphabeta TCR.