Cited by 380Immunotherapy and Immune ResponsesImmune Response and InflammationT-cell and B-cell Immunology

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Apolipoprotein-mediated pathways of lipid antigen presentation

Elzen, Peter van den, Garg, Salil, León, Luis, Brigl, Manfred, Leadbetter, Elizabeth A., Gumperz, Jenny E., Dascher, Chris C., Cheng, Tan-Yun, Sacks, Frank M., Illarionov, Petr A., Besra, Gurdyal S., Kent, Sally C., Moody, D. Branch, Brenner, Michael B.·2005·Nature

DOI 10.1038/nature04001

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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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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: Garg, Salil
Leadbetter, Elizabeth A.
Gumperz, Jenny E.
Cheng, Tan-Yun
Sacks, Frank M.
Illarionov, Petr A.
Besra, Gurdyal S.
Kent, Sally C.
Moody, D. Branch
Brenner, Michael B.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2005-10
Volume: 437
Issue: 7060
Pages: 906-910
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature04001
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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