Lipid antigens

Lipid antigens are lipid-based molecules (i.e. fat molecules or fat-like substances) that can be recognized by the immune system as antigens - i.e. they can trigger an immune response, just like proteins or sugars. Lipid antigens are not presented in the "normal way" via MHC, but via their own presentation platform: the CD1 molecules.

CD1 isoforms are MHC class I-like molecules that present lipid antigens to T cells and are associated with a variety of immune responses. CD1 molecules present lipid antigens to T cells at early stages of the immune response. The molecular details of the initial transport and loading of lipids onto CD1 proteins are not yet fully understood. There are different CD1 isoforms (CD1a-e), each of which can recognize different lipid antigens.

Apparently, lipid- and pH-dependent dynamic changes in three exposed tryptophans of the CD1 molecule are responsible for the loading of the CD1 molecules (Cuevas-Zuviría B et al. 2020). CD1a and CD1c largely mirrored the cellular lipidome, while CD1b and CD1d showed a preference for sphingolipids.

Each CD1 isoform has unique lipid species, suggesting distinct roles in lipid presentation and immune responses (Szoke-Kovacs R et al. 2024).1

Lipid antigens are:

• Components of cellular membranes or cell walls (e.g. of bacteria, fungi or tumor cells)
• Non-proteinogenic antigens that are presented on CD1 molecules
• Important for the activation of certain T cells (e.g. iNKT cells)

1. Cuevas-Zuviría B et al. (2020) Structural Dynamics of the Lipid Antigen-Binding Site of CD1d Protein. Biomolecules 10:532.
2. Szoke-Kovacs R et al. (2024) Insights into the CD1 lipidome. Front Immunol 15:1462209.