Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules.
Lipid antigens are presented to T cells by the non-polymorphic MHC class I-related CD1 molecules. Microsomal triglyceride transfer protein (MTP) is an endoplasmic reticulum (ER)-resident chaperone that has been shown to lipidate the group 2 CD1 molecule CD1d and thus to regulate its function. We now report that MTP also regulates the function of group 1 CD1 molecules CD1a, CD1b, and CD1c. Pharmacological inhibition of MTP in monocyte-derived dendritic cells and lymphoblastoid B cell lines transfected with group 1 CD1 resulted in a substantial decrease in endogenous self lipid antigen presentation to several CD1-restricted T cell lines. Silencing MTP expression in CD1c-transfected HeLa cells similarly resulted in decreased self reactivity. Unexpectedly, inhibition of ER-resident MTP, which was confirmed by confocal microscopy, also markedly decreased presentation of exogenous, endosomally loaded, mycobacterial lipid antigens by CD1a and CD1c to T cells. Thus, these studies indicate that MTP, despite its ER localization, regulates endogenous as well as exogenous lipid antigen presentation, and suggest a broad role for MTP in the regulation of CD1 antigen presentation.
Kaser
Arthur
A
Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Hava
David L
DL
Dougan
Stephanie K
SK
Chen
Zhangguo
Z
Zeissig
Sebastian
S
Brenner
Michael B
MB
Blumberg
Richard S
RS
D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans
D018949:Antigens, CD1; C437944:CD1C protein, human; C419393:CD1a antigen; C419394:CD1b antigen; D002352:Carrier Proteins; D006023:Glycoproteins; C106092:microsomal triglyceride transfer protein