Cd1

CD1, Cluster of differentiation 1, consists of a family of several human glycoproteins that are expressed on the surface of various antigen-present cells. They belong to the so-called MHC-like glycoproteins and occur in humans in 5 different isoforms: CD1a-CD1e. The coding gene is located on chromosome 1 q22-q23.

CD1 glycoproteins are divided into 2 groups:

• Group 1: CD1a, CD1b and CD1c - these glycoproteins are expressed by antigen-presenting cells.
• Group 2: CD1d - this glycoprotein is expressed by a large number of different cells.
• CD1e: intermediate, intracellular form of CD1 - this protein is not expressed on the cell surface. The function of CD1e is still unclear.

CD1 is expressed in the endoplasmic reticulum (ER) by most B cells, but also by epithelial cells. CD1a-c is also found on dendritic cells. In the endoplasmic reticulum, the CD1 proteins are assembled and loaded with lipids.

The quaternary structure of the CD1 molecule is very similar to that of the MHC complex. It is composed of several segments that form an antigen-binding groove, similar to the MHC-1 complex, which is made up of hydrophobic amino acids.

The CD1 molecule binds and presents exogenous lipid antigens of various lipid classes such as glycolipids, phospholipids, sphingolipids, etc. so that they can be recognized by T cell receptors.

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.

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). Mycobacterial lipids are preferentially processed and presented by CD1a-CD1c.

There is evidence for a potential role of adipose tissue-derived CD1-presented lipid antigens in autoimmunity (Frasca D et al. 2020). For example, adipocytes from obese mice express CD1d and thus contribute to the induction of an autoreactive immune response. In healthy human skin, there appears to be competition between permissive and blocking lipids for presentation by CD1a, the balance of which can modulate T cell responses. For example, the presentation of very long-chain fatty acids, such as certain sphingomyelin lipids by CD1a, prevents the binding of CD1a-targeted autoreactive T cells. A disturbance of this balance could favor the development of autoimmune processes.

The CD1 presentation pathway is important for antimicrobial defence.

1. Cuevas-Zuviría B et al. (2020) Structural Dynamics of the Lipid Antigen-Binding Site of CD1d Protein. Biomolecules 10:532.

2. Frasca D et al. (2020) Identification and characterization of adipose tissue-derived human antibodies with "anti-self" specificity. Front Immunol 11:392.

3. Szoke-Kovacs R et al. (2024) Insights into the CD1 lipidome. Front Immunol 15:1462209.