Abstract:
: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.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Kaser A,Hava DL,Dougan SK,Chen Z,Zeissig S,Brenner MB,Blumberg RSdoi
10.1002/eji.200738102subject
Has Abstractpub_date
2008-08-01 00:00:00pages
2351-9issue
8eissn
0014-2980issn
1521-4141journal_volume
38pub_type
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