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

Int Immunol. 2005 Jul;17(7):899-908. doi: 10.1093/intimm/dxh269. Epub 2005 Jun 20.

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 alpha-galactosylceramide (biotin-alpha-GalCer) results in enhanced murine CD1d-mediated presentation as compared with presentation of non-targeted biotin-alpha-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation / drug effects
  • Antigen Presentation / immunology*
  • Antigens, CD1 / immunology*
  • Antigens, CD1d
  • Biotin / analogs & derivatives*
  • Biotin / immunology
  • Biotin / pharmacology
  • Cell Line
  • Endosomes / immunology*
  • Enzyme Precursors / antagonists & inhibitors
  • Enzyme Precursors / immunology
  • Galactosylceramides / immunology*
  • Galactosylceramides / pharmacology
  • Histocompatibility Antigens Class I / immunology
  • Intracellular Signaling Peptides and Proteins
  • Killer Cells, Natural / immunology
  • Mice
  • Protein Transport / drug effects
  • Protein Transport / immunology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / immunology
  • Receptors, Antigen, B-Cell / immunology*
  • Stilbenes / pharmacology
  • Syk Kinase
  • T-Lymphocytes / immunology

Substances

  • Antigens, CD1
  • Antigens, CD1d
  • Enzyme Precursors
  • Galactosylceramides
  • Histocompatibility Antigens Class I
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Antigen, B-Cell
  • Stilbenes
  • biotin-galactosylceramide
  • 3,3',4,5'-tetrahydroxystilbene
  • Biotin
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse