Another View of T Cell Antigen Recognition: Cooperative Engagement of Glycolipid Antigens by Va14Ja18 Natural TCR

Aleksandar K. Stanic, R. Shashidharamurthy, Jelena S. Bezbradica, Naoto Matsuki, Yoshitaka Yoshimura, Sachiko Miyake, Eun Young Choi, Todd D. Schell, Luc Van Kaer, Satvir S. Tevethia, Derry C. Roopenian, Takashi Yamamura, Sebastian Joyce

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Va14Ja18 natural T (iNKT) cells rapidly elicit a robust effector response to different glycolipid Ags, with distinct functional outcomes. Biochemical parameters controlling iNKT cell function are partly defined. However, the impact of iNKT cell receptor β-chain repertoire and how α-galactosylceramide (α-GalCer) analogues induce distinct functional responses have remained elusive. Using altered glycolipid ligands, we discovered that the Vb repertoire of iNKT cells impacts recognition and Ag avidity, and that stimulation with suboptimal avidity Ag results in preferential expansion of high-affinity iNKT cells. iNKT cell proliferation and cytokine secretion, which correlate with iNKT cell receptor down-regulation, are induced within narrow biochemical thresholds. Multimers of CD1d1-αGalCer- and αGalCer analogue-loaded complexes demonstrate cooperative engagement of the Va14Ja18 iNKT cell receptor whose structure and/ or organization appear distinct from conventional αβ TCR. Our findings demonstrate that iNKT cell functions are controlled by affinity thresholds for glycolipid Ags and reveal a novel property of their Ag receptor apparatus that may have an important role in iNKT cell activation.

Original languageEnglish (US)
Pages (from-to)4539-4551
Number of pages13
JournalJournal of Immunology
Issue number9
StatePublished - Oct 1 2003

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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