Lipid metabolism, atherogenesis and CD1-restricted antigen presentation.
CD1 molecules are a family of major histocompatibility complex (MHC)-related glycoproteins that present lipid and glycolipid antigens to T cells. Interestingly, it has been demonstrated that CD1d-restricted T cells have a pathogenic role in atherosclerosis. Recent studies suggest an association between the cellular machinery that loads CD1 molecules with glycolipids and several key proteins in lipid metabolism. These proteins include the sphingolipid activator proteins (SAPs), microsomal triglyceride transfer protein (MTP) and apolipoprotein E (apoE). MTP and SAPs seem to be crucial for loading CD1d with lipids in the endoplasmic reticulum and endosomal compartments, respectively, whereas apoE facilitates efficient uptake and delivery of exogenous lipid antigens to CD1d in endosomal compartments. These studies reveal new and unexpected relationships between lipid metabolism and antigen presentation by CD1 molecules. Targeting this pathway of immune activation might have therapeutic potential for the treatment of chronic inflammatory diseases.
Major
Amy S
AS
Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, 2220 Pierce Avenue, Room 383, Preston Research Building, Nashville, TN 37232, USA. amy.major@vanderbilt.edu
Joyce
Sebastian
S
Van Kaer
Luc
L
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D049289:G(M2) Activator Protein / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood / Q000276:immunology; D049231:Saposins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D018949:Antigens, CD1; D001057:Apolipoproteins E; D002352:Carrier Proteins; D016207:Cytokines; D049289:G(M2) Activator Protein; D008055:Lipids; D049231:Saposins; C106092:microsomal triglyceride transfer protein