Premium
Presentation of α‐galactosylceramide by murine CD1d to natural killer T cells is facilitated by plasma membrane glycolipid rafts
Author(s) -
Lang Gillian A.,
Maltsev Sergei D.,
Besra Gurdyal S.,
Lang Mark L.
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01896.x
Subject(s) - cd1d , cd1 , natural killer t cell , antigen presentation , glycolipid , antigen , microbiology and biotechnology , biology , lipid raft , antigen presenting cell , t cell receptor , major histocompatibility complex , t cell , chemistry , immunology , immune system , cd8 , signal transduction
Summary CD1 molecules are non‐polymorphic major histocompatibility complex class I‐related proteins that bind and present glycolipid antigens to T‐cell antigen receptors (TCR) expressed by αβ T cells or natural killer‐like T cells (NKT). Anti‐metastatic properties of NKT cells reactive to the CD1d‐binding antigen α‐galactosylceramide (α‐GalCer) are now being explored as a contributor to tumour cell killing. In this study, we tested the hypothesis that presentation of α‐GalCer by murine CD1d (mCD1d) to mCD1d‐restricted NKT cells was facilitated by plasma membrane glycolipid rafts. Confocal microscopy of mCD1d‐transfected A20 B cells (A20mCD1d) demonstrated that mCD1d was raft‐localized. This observation was confirmed by immunoblotting of raft fractions isolated on sucrose density gradients. Raft disruption by the cholesterol‐binding agent nystatin, or short‐chain ceramides, inhibited presentation of low concentrations of α‐GalCer to NKT cells. Inhibition of antigen presentation was reversed by treatment of A20mCD1d cells with higher α‐GalCer concentrations, or removal of raft‐disrupting agents. These data indicate that partitioning of mCD1d into membrane rafts increases the capacity of antigen‐presenting cells to present limiting quantities of glycolipid antigens, perhaps by stabilizing mCD1d/antigen structures on the plasma membrane and optimizing TCR engagement on NKT cells.