For members of the CD I family of β2-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 CD I trafficking and antigen presentation. However, in vitro studies with cells transfected with mutant CD I 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 CD I d cytoplasmic tail deleted. Despite adequate surface CD I d 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 CD I d cytoplasmic tail motif in vivo.
ASJC Scopus subject areas
- Immunology and Allergy