Sandbox Reserved 1660
From Proteopedia
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| - | The ligands | + | The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. These include glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules. |
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==== Immunotherapeutic tool ==== | ==== Immunotherapeutic tool ==== | ||
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| + | The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer. | ||
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==== NKT cells marker ==== | ==== NKT cells marker ==== | ||
Revision as of 15:27, 10 January 2021
| This Sandbox is Reserved from 26/11/2020, through 26/11/2021 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1643 through Sandbox Reserved 1664. |
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Structure of mouse CD1d expressed in SF9 cells, no ligand added
CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins.
Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.
Contents |
Function
Role in the immune system
CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.
Ligands presented by CD1d
The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. These include glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.
Structure
CD1d protein is made of 2 chains:
- - an alpha chain (T-cell surface glycoprotein CD1d1) of 287 amino acids
- - a beta-2-microglobulin chain of 99 amino acids.
- - an alpha chain (T-cell surface glycoprotein CD1d1) of 287 amino acids
Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.
Impact of ligand-binding
Conformational variation
NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.
CD1d affinity
Applications
Immunotherapeutic tool
The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.
NKT cells marker
CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted.
See Also
References
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