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International Immunology Advance Access originally published online on June 20, 2005
International Immunology 2005 17(7):899-908; doi:10.1093/intimm/dxh269
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

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

Gillian A. Lang1, Petr A. Illarionov2, Aharona Glatman-Freedman3, Gurdyal S. Besra2 and Mark L. Lang1

1 Department of Microbiology and Immunology, 632W Borwell Building, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA
2 School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
3 Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10461, USA

Correspondence to: M. L. Lang; E-mail: mark.l.lang{at}dartmouth.edu

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.

Keywords: antigen presentation, BCR, CD1d, {alpha}-galactosylceramide, MIIC

Transmitting editor: I. Pecht


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