The role of CD1d transmembrane and cytoplasmic tail domain in CD1d trafficking pathway

CD1 molecules are a family of MHC class I-like lipid presenting molecules. They could specifically recognize self lipid antigens and extracellular lipid antigens, and present them to T lymphocytes. T lymphocytes are stimulated to secrete different cytokines to execute their immunological functions. CD1d, a member of CD1 family, exists both in human and in mouse. It can particularly activate invariant Natural Killer T (NKT) cells which are mostly-studied non-conventional T cell types. CD1d molecule is delivered onto cell surface membrane after synthesis in Endoplasmic Reticulum (ER) and is believed to be internalized via AP-2 dependent endocytic pathway. During the trafficking route, CD1d recognizes and assembles with lipid antigens to form antigen-CD1d complex in the early endosome, the complex can be delivered onto the cell membrane after its formation. So the intracellular trafficking pathway of CD1d molecule is important for its immunological function. Based on the previous studies, tyrosine-based endosomal targeting sequence, YXXZ (where Y is tyrosine, X is any amino acid and Z is bulky hydrophobic amino acid) and some other amino acids on the cytoplasmic tail of CD1d are the major functional sites for its endocytosis process. The purpose of the thesis is to study the functions of CD1d cytoplasmic tail and transmembrane domain on its intracellular trafficking routes. The results show that the 14th amino acid from the bottom on the cytoplasmic tail may be the important site to determine CD1d molecule cell surface expression and the entire transmembrane domain is required for CD1d normal expression in cells.