Apolipoprotein-mediated pathways of lipid antigen presentation - PubMed (original) (raw)

. 2005 Oct 6;437(7060):906-10.

doi: 10.1038/nature04001.

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

Affiliations

• PMID: 16208376
• DOI: 10.1038/nature04001

Apolipoprotein-mediated pathways of lipid antigen presentation

Peter van den Elzen et al. Nature. 2005.

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.

PubMed Disclaimer

Similar articles

• Lipid metabolism, atherogenesis and CD1-restricted antigen presentation.
  Major AS, Joyce S, Van Kaer L. Major AS, et al. Trends Mol Med. 2006 Jun;12(6):270-8. doi: 10.1016/j.molmed.2006.04.004. Epub 2006 May 2. Trends Mol Med. 2006. PMID: 16651026 Review.
• Mechanisms of lipid antigen presentation by CD1.
  Jackman RM, Moody DB, Porcelli SA. Jackman RM, et al. Crit Rev Immunol. 1999;19(1):49-63. Crit Rev Immunol. 1999. PMID: 9987600 Review.
• The Third Way: Progress on pathways of antigen processing and presentation by CD1.
  Lawton AP, Kronenberg M. Lawton AP, et al. Immunol Cell Biol. 2004 Jun;82(3):295-306. doi: 10.1111/j.0818-9641.2004.01258.x. Immunol Cell Biol. 2004. PMID: 15186261 Review.
• The ins and outs of CD1 molecules: bringing lipids under immunological surveillance.
  Gumperz JE. Gumperz JE. Traffic. 2006 Jan;7(1):2-13. doi: 10.1111/j.1600-0854.2005.00364.x. Traffic. 2006. PMID: 16445682 Review.
• How the immune system detects lipid antigens.
  De Libero G, Mori L. De Libero G, et al. Prog Lipid Res. 2010 Apr;49(2):120-7. doi: 10.1016/j.plipres.2009.10.002. Epub 2009 Oct 24. Prog Lipid Res. 2010. PMID: 19857519 Review.

Cited by

• Infection of macrophages with Mycobacterium tuberculosis induces global modifications to phagosomal function.
  Podinovskaia M, Lee W, Caldwell S, Russell DG. Podinovskaia M, et al. Cell Microbiol. 2013 Jun;15(6):843-59. doi: 10.1111/cmi.12092. Epub 2013 Jan 9. Cell Microbiol. 2013. PMID: 23253353 Free PMC article.
• Are human iNKT cells keeping tabs on lipidome perturbations triggered by oxidative stress in the blood?
  Felley L, Gumperz JE. Felley L, et al. Immunogenetics. 2016 Aug;68(8):611-22. doi: 10.1007/s00251-016-0936-8. Epub 2016 Jul 8. Immunogenetics. 2016. PMID: 27393663 Free PMC article. Review.
• Models Contribution to the Understanding of Sarcoidosis Pathogenesis: "Are There Good Models of Sarcoidosis?".
  Besnard V, Jeny F. Besnard V, et al. J Clin Med. 2020 Jul 31;9(8):2445. doi: 10.3390/jcm9082445. J Clin Med. 2020. PMID: 32751786 Free PMC article. Review.
• Serum Apolipoprotein E and Other Inflammatory Markers Can Identify Non-Responding Patients to a Dendritic Cell Vaccine.
  Leeman H, Kaminska E, Green D, Bodman-Smith M, Gravett A, Bodman-Smith K, Copier J, Coulton G, Fusi A, Dalgleish AG. Leeman H, et al. Transl Oncol. 2019 Mar;12(3):397-403. doi: 10.1016/j.tranon.2018.11.002. Epub 2018 Dec 8. Transl Oncol. 2019. PMID: 30530187 Free PMC article.
• Invariant natural killer T cells in rheumatic disease: a joint dilemma.
  Drennan MB, Aspeslagh S, Elewaut D. Drennan MB, et al. Nat Rev Rheumatol. 2010 Feb;6(2):90-8. doi: 10.1038/nrrheum.2009.261. Nat Rev Rheumatol. 2010. PMID: 20125176 Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group
  • Ovid Technologies, Inc.

• Other Literature Sources

  • The Lens - Patent Citations Database

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal