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Immunology Letters 117 (2008) 1–8
Presentation of lipid antigens to T cells
Lucia Mori, Gennaro De Libero ∗
Experimental Immunology, Department of Research, University Hospital, Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland Received 20 November 2007; received in revised form 28 November 2007; accepted 30 November 2007 Availableonline 15 January 2008
Abstract T cells speciﬁc for lipid antigens participate in regulation of the immune response during infections, tumor immunosurveillance, allergy and autoimmune diseases. T cells recognize lipid antigens as complexes formed with CD1 antigen-presenting molecules, thus resembling recognition of MHC-peptide complexes. The biophysical properties of lipids impose uniquemechanisms for their delivery, internalization into antigen-presenting cells, membrane trafﬁcking, processing, and loading of CD1 molecules. Each of these steps is controlled at molecular and celular levels and determines lipid immunogenicity. Lipid antigens may derive from microbes and from the cellular metabolism, thus allowing the immune system to survey a large repertoire of immunogenic molecules.Recognition of lipid antigens facilitates the detection of infectious agents and the initiation of responses involved in immunoregulation and autoimmunity. This review focuses on the presentation mechanisms and speciﬁc recognition of self and bacterial lipid antigens and discusses the important open issues. © 2007 Elsevier B.V. All rights reserved.
Keywords: Antigen presentation; T cells; CD1;Lipid antigens
1. Introduction The mode how B and T lymphocytes recognize lipid antigens differs greatly. B cells use membrane-bound antibodies and interact with the hydrophilic heads of glycolipids and recognize exposed shapes of the molecules. T cells instead use the TCR or and recognize complexes formed by lipids associated with dedicated antigen-presenting molecules, which belong to theCD1 family. In humans there are 5 CD1 genes, which encode 5 proteins, CD1a, b, c d and e. The presentation mechanism of lipids has physical requirements dictated by the very nature of lipids. As lipids are poorly soluble in water they are always associated with membranes or with lipid-transfer proteins (LTP) in tissues and biological ﬂuids, and from here comes the importance of lipid-bindingproteins in lipid uptake by antigen-presenting cells (APC), in lipid transport inside cells and in lipid handling until CD1 loading. Secondly, different CD1 isoforms show overlapping, but also different lipid-binding speciﬁcity, and this has a direct impact on the repertoire of lipid antigens that stimulate T cells. Thirdly, the intracellular compartmentalization of lipids may facilitate or hindertheir capacity to
form complexes with CD1 molecules, thus directly contributing to lipid immunogenicity. The structure of CD1 molecules, their trafﬁcking capacity as well as the structures of immunogenic lipids have been exhaustively described in a variety of reviews and therefore will not be discussed here. 2. Presentation of lipid antigens Lipid immunogenicity depends on a coordinatedseries of events, which start with cellular uptake and ends with the generation of stable CD1-lipid complexes expressed on the surface of APC. Here, each of the steps involved in lipid antigen presentation is illustrated and the most important open issues are discussed. 2.1. Delivery and internalization of extracellular lipids Two important steps in lipid antigen presentation are the lipiddelivery to different tissues and lipid internalization by APC. Because of their hydrophobicity, lipids circulate in association with LTP or are transported within membranes. The transport of extracellular lipid antigens within serum is mediated by lipoproteins such as high density (HDL) and very low density (VLDL)
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