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The Ins and Outs of CD1 Molecules: Bringing Lipids Under Immunological Surveillance
Author(s) -
Gumperz Jenny E.
Publication year - 2006
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2005.00364.x
Subject(s) - cd1 , endosome , biology , cd1d , microbiology and biotechnology , antigen , antigen presentation , intracellular , immune system , antigen presenting cell , t cell , immunology , natural killer t cell , cd8
An emerging area of investigation is the role of lipids as immunological antigens. CD1 glycoproteins comprise a family of molecules that are specialized for presenting lipids, glycolipids and lipopeptides to T lymphocytes. Variations in the cytoplasmic tail sequences of CD1 isoforms lead to differential association with adaptor proteins and consequently divergent routes of intracellular trafficking, resulting in surveillance of distinct cellular sites for binding lipid antigens. CD1 molecules efficiently gain access to lipids from intracellular microbial pathogens in endosomal compartments, and the trafficking and lipid‐binding specialization of CD1 isoforms may correlate with the endosomal segregation of structurally distinct lipids. Endosomal trafficking is also critical for CD1d molecules to load antigenic self‐lipids that are presented to autoreactive CD1d‐restricted natural killer (NK)T cells and is required for the positive selection of these unique T cells. Recent studies reveal a key role for accessory proteins that facilitate the uptake of lipid antigens by CD1 molecules. These include lysosomal lipid‐transfer proteins, such as the saposins, and apolipoprotein E, the major serum factor that binds and delivers extracellular lipids to antigen‐presenting cells. These advances in understanding the CD1 lipid antigen presentation system raise new considerations about the role of the immune response in lipid‐related diseases.