BCR targeting of biotin-α-galactosylceramide leads to enhanced presentation on CD1d and requires transport of BCR to CD1d-containing endocytic compartments

Gillian A. Lang, Petr A. Illarionov, Aharona Glatman-Freedman, Gurdyal S. Besra, Mark L. Lang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

CD1d is a non-polymorphic MHC class I-related protein that binds and presents glycolipid antigens to T cell antigen receptors expressed by NK-like T (NKT) cells. CD1d-dependent immune responses play critical roles in infectious disease, autoimmunity, allergy and cancer. We tested the hypothesis that B cell antigen receptor (BCR) targeting of a biotin-modified version of the CD1d-binding antigen α-galactosylceramide (biotin-α-GalCer) results in enhanced murine CD1d-mediated presentation as compared with presentation of non-targeted biotin-α-GalCer. Presentation of BCR-targeted antigen to NKT cells was enhanced 100- to 1000-fold compared with non-targeted antigen. CD1d presentation of BCR-targeted antigen was observed after 4 h treatment, consistent with a requirement for endosomal trafficking. Furthermore, unlike non-targeted antigen, BCR-targeted antigen was not loaded directly onto cell-surface CD1d. Blocking BCR signaling with the Syk tyrosine kinase inhibitor piceatannol inhibited presentation of BCR-targeted antigen but not non-targeted antigen. Piceatannol blocked transport of the BCR to CD1d-containing endosomes, showing that intersection of BCR-targeted antigen with endosomes is required for enhanced mCD1d antigen presentation. Our data suggest that the BCR facilitates capture of low quantities of mCD1d antigens to enhance CD1d-dependent immune responses.

Original languageEnglish
Pages (from-to)899-908
Number of pages10
JournalInternational Immunology
Volume17
Issue number7
DOIs
StatePublished - Jul 2005
Externally publishedYes

Keywords

  • Antigen presentation
  • BCR
  • CD1d
  • MIC
  • α-galactosylceramide

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