Multiple defects in antigen presentation and T cell development by mice expressing cytoplasmic tail-truncated CD1d.
For members of the CD1 family of beta(2)-microglobulin-associated lipid-presenting molecules, tyrosine-based motifs in the cytoplasmic tail and invariant chain (Ii) govern glycoprotein trafficking through endosomal compartments. Little is known about the intracellular pathways of CD1 trafficking and antigen presentation. However, in vitro studies with cells transfected with mutant CD1 that had a truncated cytoplasmic tail have suggested a role for these tyrosine motifs in some, but not all, antigenic systems. By introducing a deletion of the tyrosine motif into the germ line, and through homologous recombination in embryonic stem cells, we now describe knock-in mice with the CD1d cytoplasmic tail deleted. Despite adequate surface CD1d expression and the presence of Ii, these mutant mice showed multiple and selective abnormalities in intracellular trafficking, antigen presentation and T cell development, demonstrating the critical functions of the CD1d cytoplasmic tail motif in vivo.
Chiu
Ya-Hui
YH
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Park
Se-Ho
SH
Benlagha
Kamel
K
Forestier
Claire
C
Jayawardena-Wolf
Jayanthi
J
Savage
Paul B
PB
Teyton
Luc
L
Bendelac
Albert
A
D020816:Amino Acid Motifs; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000941:Antigens / Q000276:immunology; D018949:Antigens, CD1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000276:immunology; D001692:Biological Transport; D019921:Biotinylation; D017637:Clonal Deletion; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000276:immunology; D011992:Endosomes / Q000378:metabolism; D005260:Female; D005699:Galactosylceramides / Q000276:immunology; D018390:Gene Targeting; D006825:Hybridomas / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019000:Phosphotyrosine / Q000502:physiology*; D021381:Protein Transport; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D017384:Sequence Deletion; D013047:Specific Pathogen-Free Organisms; D013234:Stem Cells; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D014162:Transfection
D000941:Antigens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine