CD1d endosomal trafficking is independently regulated by an intrinsic CD1d-encoded tyrosine motif and by the invariant chain.
Endosomal trafficking is an essential component of the CD1 pathway of lipid antigen presentation to T cells. We demonstrate that CD1d access to endosomal compartments is under dual regulation by an intrinsic tyrosine-based motif, which governs intense recycling between the plasma membrane and the endosome, and by the invariant chain, with which CD1d associates in the endoplasmic reticulum. Both pathways independently enhance antigen presentation to V(alpha)14(+) NKT cells, the main subset of CD1d-restricted T cells. These results reveal the complexity of CD1d trafficking and suggest that the invariant chain was a component of ancestral antigen presentation pathways prior to the evolution of MHC and CD1.
Jayawardena-Wolf
J
J
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Benlagha
K
K
Chiu
Y H
YH
Mehr
R
R
Bendelac
A
A
D020816:Amino Acid Motifs; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D018949:Antigens, CD1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055610:Antigens, CD1d; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D000954:Antigens, Surface / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D019921:Biotinylation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D019143:Evolution, Molecular; D005347:Fibroblasts / Q000378:metabolism; D006031:Glycosylation; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006825:Hybridomas / Q000378:metabolism; D007700:Kinetics; D016393:Lymphoma, B-Cell / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; C045084:invariant chain; D014443:Tyrosine