Structure-Function Implications of the Ability of Monoclonal Antibodies Against α-Galactosylceramide-CD1d Complex to Recognize β-Mannosylceramide Presentation by CD1d

Katharine Clark, Jessica Yau, Anja Bloom, Jing Wang, David J. Venzon, Motoshi Suzuki, Lise Pasquet, Benjamin J. Compton, Susanna L. Cardell, Steven A. Porcelli, Gavin F. Painter, Dirk M. Zajonc, Jay A. Berzofsky, Masaki Terabe

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

iNKT cells are CD1d-restricted T cells recognizing lipid antigens. The prototypic iNKT cell-agonist α-galactosylceramide (α-GalCer) alongside compounds with similar structures induces robust proliferation and cytokine production of iNKT cells and protects against cancer in vivo. Monoclonal antibodies (mAbs) that detect CD1d-α-GalCer complexes have provided critical information for understanding of antigen presentation of iNKT cell agonists. Although most iNKT cell agonists with antitumor properties are α-linked glycosphingolipids that can be detected by anti-CD1d-α-GalCer mAbs, β-ManCer, a glycolipid with a β-linkage, induces strong antitumor immunity via mechanisms distinct from those of α-GalCer. In this study, we unexpectedly discovered that anti-CD1d-α-GalCer mAbs directly recognized β-ManCer-CD1d complexes and could inhibit β-ManCer stimulation of iNKT cells. The binding of anti-CD1d-α-GalCer mAb with β-ManCer-CD1d complexes was also confirmed by plasmon resonance and could not be explained by α-anomer contamination. The binding of anti-CD1d-α-GalCer mAb was also observed with CD1d loaded with another β-linked glycosylceramide, β-GalCer (C26:0). Detection with anti-CD1d-α-GalCer mAbs indicates that the interface of the β-ManCer-CD1d complex exposed to the iNKT cell TCR can assume a structure like that of CD1d-α-GalCer, despite its disparate carbohydrate structure. These results suggest that certain β-linked monoglycosylceramides can assume a structural display similar to that of CD1d-α-GalCer and that the data based on anti-CD1d-α-GalCer binding should be interpreted with caution.

Original languageEnglish (US)
Article number2355
JournalFrontiers in immunology
Volume10
DOIs
StatePublished - Oct 9 2019

Keywords

  • CD1d
  • L363
  • alpha-galactosylceramide
  • beta-mannosylceramide
  • natural killer T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Clark, K., Yau, J., Bloom, A., Wang, J., Venzon, D. J., Suzuki, M., Pasquet, L., Compton, B. J., Cardell, S. L., Porcelli, S. A., Painter, G. F., Zajonc, D. M., Berzofsky, J. A., & Terabe, M. (2019). Structure-Function Implications of the Ability of Monoclonal Antibodies Against α-Galactosylceramide-CD1d Complex to Recognize β-Mannosylceramide Presentation by CD1d. Frontiers in immunology, 10, [2355]. https://doi.org/10.3389/fimmu.2019.02355