Glycolipid Presentation by CD1


CD1 molecules constitute a family of nonpolymorphic, MHC class I‐like antigen‐presenting glycoproteins, which bind amphipathic lipid antigens and present them to T cells. These proteins are involved in presenting a broad range of self and foreign lipid antigens to variable T lymphocytes and natural killer T cells bearing a semi‐invariant T‐cell receptor (iNKT). It has become clear that the recognition of lipid antigens by T cells plays an important role in the detection and clearance of pathogens, immune response regulation and tissue surveillance.

Key Concepts

  • Self and microbial lipids and glycolipids are recognised by T cells.
  • Hydrophobic pockets of CD1 proteins allow lipid antigens to be loaded via their alkyl chains, while the hydrophilic part of the antigen is presented to T‐cell receptors.
  • CD1 proteins are non‐polymorphic and predominantly expressed on the surface of antigen‐presenting cells.
  • Glycolipids can be processed into smaller antigenic structures in the endosomal pathway.
  • CD1e, a soluble protein found in late endosomes, assists in lipid antigen editing and loading onto other CD1 proteins.
  • CD1‐restricted T cells express αβ or γδ TCR and are found in CD4+, CD8+ or double‐negative T‐cell populations.
  • The frequency of autoreactive T cells is high among CD1‐restricted T cells.

Keywords: lipid; glycolipid; antigen; CD1; presentation; processing; saposin; endosome; lymphocyte T; Mycobacterium tuberculosis

Figure 1. Overview of lipid antigen presentation by CD1 proteins. Following their biosynthesis, CD1a, b, c and d are expressed at the surface of antigen‐presenting cells before being recycled to different endosomal compartments, in which they encounter lipids acquired from extracellular sources. Late endosomes and lysosomes are acidic compartment rich in accessory proteins and enzymes, facilitating the editing of lipid antigens and the loading of CD1 binding sites with these antigens.
Figure 2. Structural characteristics of CD1 proteins. (a) Structure of the CD1b protein – lateral view (left), and a corresponding top view (right). Three extracellular domains of CD1b (α1, α2 and α3) noncovalently associate with β2 microglobulin (β2m) (light gray). Domains engaged in antigen binding are shown in colour: α1 – red, α2 – green. The walls of the antigen binding groove are formed by helices and the floor consists of a β‐sheet. (b) Schematic representation of the mode of binding of the amphipathic antigen within the CD1b groove. (c) Summary of the major structural features of individual CD1 molecules.
Figure 3. The structural diversity of lipid antigens presented by CD1 proteins. CD1 isoforms present lipid antigens with diverse hydrophobic and head group moieties.
Figure 4. Processing of PIM antigens and their loading onto CD1 proteins. CD1e, exclusively found in late endosome and lysosome, is an accessory protein of the lipid antigens processing. CD1e facilitates the enzymatic modification of lipid antigens and their loading onto CD1 proteins by acting as a lipid transfer protein.
Figure 5. CD1‐restricted T‐cell functions. CD1‐restricted T cells contribute to immune responses by producing cytokines and exerting cytotoxicity mediated by the release of perforin and granulysin. Group 1 and 2 CD1‐restricted T cells include self‐reactive T cells and T cells specifically recognising microbial lipids. iNKT cells, constituting a major population of CD1d‐restricted T cells, are innate‐like T lymphocytes activated during microbial infection, through either the TCR‐mediated direct recognition of the CD1d‐microbial lipid complex or indirectly, by the cytokine environment generated by innate immune cells.


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Further Reading

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Moody DB (ed) (2007) T Cell Activation by CD1 and Lipid Antigens, p. 345. Berlin Heidelberg: Springer‐Verlag.

Van Rhijn I and Moody DB (2015b) CD1 and mycobacterial lipids activate human T cells. Immunological Reviews 264: 138–153.

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Layre, Emilie, Mazurek, Jolanta, and Gilleron, Martine(Aug 2015) Glycolipid Presentation by CD1 . In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020182.pub2]