Apolipoprotein-mediated pathways of lipid antigen presentation.
Peptide antigens are presented to T cells by major histocompatibility complex (MHC) molecules, with endogenous peptides presented by MHC class I and exogenous peptides presented by MHC class II. In contrast to the MHC system, CD1 molecules bind lipid antigens that are presented at the antigen-presenting cell (APC) surface to lipid antigen-reactive T cells. Because CD1 molecules survey endocytic compartments, it is self-evident that they encounter antigens from extracellular sources. However, the mechanisms of exogenous lipid antigen delivery to CD1-antigen-loading compartments are not known. Serum apolipoproteins are mediators of extracellular lipid transport for metabolic needs. Here we define the pathways mediating markedly efficient exogenous lipid antigen delivery by apolipoproteins to achieve T-cell activation. Apolipoprotein E binds lipid antigens and delivers them by receptor-mediated uptake into endosomal compartments containing CD1 in APCs. Apolipoprotein E mediates the presentation of serum-borne lipid antigens and can be secreted by APCs as a mechanism to survey the local environment to capture antigens or to transfer microbial lipids from infected cells to bystander APCs. Thus, the immune system has co-opted a component of lipid metabolism to develop immunological responses to lipid antigens.
van den Elzen
Peter
P
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Garg
Salil
S
León
Luis
L
Brigl
Manfred
M
Leadbetter
Elizabeth A
EA
Gumperz
Jenny E
JE
Dascher
Chris C
CC
Cheng
Tan-Yun
TY
Sacks
Frank M
FM
Illarionov
Petr A
PA
Besra
Gurdyal S
GS
Kent
Sally C
SC
Moody
D Branch
DB
Brenner
Michael B
MB
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D011973:Receptors, LDL / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D018949:Antigens, CD1; D001057:Apolipoproteins E; D008055:Lipids; D011973:Receptors, LDL