CD1D

What is CD1D protein?

CD1D (CD1d molecule) gene is a protein coding gene which situated on the long arm of chromosome 1 at locus 1q23. This gene encodes a divergent member of the CD1 family of transmembrane glycoproteins, which are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. The protein encoded by this gene localizes to late endosomes and lysosomes via a tyrosine-based motif in the cytoplasmic tail. The CD1D protein is consisted of 335 amino acids and its molecular mass is approximately 37.7 kDa.

What is the function of CD1D protein?

CD1d functions as an antigen-presenting protein that binds to self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells (NKT cells). CD1d is involved in the regulation of the immune response, particularly in the activation of invariant NKT cells. It plays a role in presenting glycolipid antigens to these cells, which are equipped with natural killer receptors and an invariant T-cell receptor-alpha chain. Recent studies have shown that CD1d has a function in the control of lipid metabolism, with CD1d-deficient macrophages exhibiting altered metabolic profiles. The acquisition of glycolipid antigens by CD1d occurs in part in endosomes through the function of resident lipid transfer proteins, such as saposins.

Fig1. Roles of iNKT cells and Th2 cells in the development of AHR and airway inflammation. (Chiaki Iwamura, 2018)

CD1D Related Signaling Pathway

CD1d can mediate reverse signaling in antigen-presenting cells (APCs), which may influence the activation and function of these cells. CD1d presents lipid antigens to natural killer T cells (NKT cells), which are equipped with an invariant T-cell receptor (TCR). This interaction is crucial for the activation of NKT cells, which play a role in autoimmune diseases, tumor rejection, and certain microbial infections. CD1d regulates the internalization of the lipid transporter CD36, which is involved in lipid uptake and metabolism in macrophages. This regulation by CD1d affects the inflammatory-metabolic circuit in these cells.

CD1D Related Diseases

CD1d has been implicated in the regulation of tumor growth. In some studies, CD1d deficiency has been associated with increased tumor growth, while in others, it has been shown to inhibit tumor progression. The specific role of CD1d in cancer appears to be context-dependent and may involve the activation of NKT cells and their influence on the immune response to tumors. CD1d is involved in the regulation of immune responses, and dysregulation of CD1d expression or function could contribute to autoimmune diseases. CD1d and NKT cells can influence the immune response to infections. CD1d has been shown to play a role in the control of lipid metabolism in macrophages, which could have implications for metabolic diseases. CD1d deficiency in macrophages leads to metabolic reprogramming, which primes these cells for enhanced responses to innate signals.

Bioapplications of CD1D

The CD1d protein is able to activate NKT cells, which play a role in immune regulation, anti-tumor and anti-pathogen activity. iNKT cell-based therapies have shown safety and clinical activity in some cancers. Tri-specific CD1d-Vd2 bsTCE (LAVA-051) is being tested in Phase 1/2a clinical trials for the treatment of patients with AML, CLL, and MM. In addition, the CD1d recombinant protein has the potential to regulate immunity and may be used to develop new immunotherapeutic strategies.