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Apolipoprotein-mediated pathways of lipid antigen presentation
Abstract
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.
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“Moreover, it was shown recently that apoE mediates the presentation of lipid antigens to the immune system and in this way influences the inflammatory process [ 11].”
From ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age (2006) · cites this paper as [11]
In the citing paper
“Although it is interesting to note that apoE is involved in the presentation of exogenous lipid antigens (van den Elzen et al., 2005), how apoE exerts its effects on immune responses still remains unclear.”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as van den Elzen et al., 2005
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Metadata
- Authors
- Elzen, P. V. D., Garg, S., León, L., Brigl, M., Leadbetter, E. A., Gumperz, J. E., Dascher, C. C., Cheng, T.-Y., Sacks, F. M., Illarionov, P. A., Besra, G. S., Kent, S. C., Moody, D. B., & Brenner, M. B.
- Affiliations
- Harvard University (US)
- University of Birmingham (GB)
- Brigham and Women's Hospital (US)
- Corresponding author
- Brenner, Michael B.
- ORCID
- Venue
- Nature
- Published
- 2005-10
- Volume
- 437
- Issue
- 7060
- Pages
- 906-910
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2061503084
- Cited by
- 380
- References
- 28
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 9 · 2023: 12 · 2022: 10 · 2021: 16 · 2020: 10 · 2019: 5 · 2018: 21 · 2017: 21 · 2016: 19 · 2015: 22 · 2014: 21 · 2013: 19 · 2012: 20
- FWCI
- 10.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Wellcome Trust
- National Heart, Lung, and Blood Institute (R01HL071590)
- National Institute of General Medical Sciences (T32GM007753)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- apolipoprotein E, lipid antigen presentation, T cell activation, antigen-presenting cells, lipid metabolism, atherosclerosis, autoimmunity, receptor-mediated uptake, MHC class I and II
- MeSH terms
- Animals, Antigen-Presenting Cells, Apolipoproteins E, Dendritic Cells, Humans, Lipids, Lymphocyte Activation, Receptors, LDL, Endosomes, T-Lymphocytes, Antigen Presentation, Antigens, CD1, Lipid Metabolism, Mice
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