TY - JOUR
T1 - BCR targeting of biotin-alpha-galactosylceramide leads to enhanced presentation on CD1d and requires transport of BCR to CD1d-containing endocytic compartments
AU - Lang, GA
AU - Illarionov, Petr
AU - Glatman-Freedman, A
AU - Besra, Gurdyal
AU - Lang, ML
PY - 2005/5/20
Y1 - 2005/5/20
N2 - 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.
AB - 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.
KW - alpha-galactosylceramide
KW - BCR
KW - antigen presentation
KW - MIIC
KW - CD1d
UR - http://www.scopus.com/inward/record.url?scp=26444517845&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxh269
DO - 10.1093/intimm/dxh269
M3 - Article
C2 - 15967785
SN - 1460-2377
VL - 17
SP - 899
EP - 908
JO - International Immunology
JF - International Immunology
IS - 7
ER -