Invariant Chain

Definition

The invariant chain is a protein that plays a crucial role in the assembly and trafficking of major histocompatibility complex (MHC) class II molecules. It is essential for the proper functioning of antigen-presenting cells in the immune system.

5 Must Know Facts For Your Next Test

1. The invariant chain associates with newly synthesized MHC class II molecules in the endoplasmic reticulum, preventing the binding of self-peptides and directing the complex to the endosomal/lysosomal compartment.
2. The invariant chain contains a targeting signal that guides the MHC class II-invariant chain complex to specialized endocytic compartments where antigenic peptides are loaded onto the MHC class II molecules.
3. The invariant chain is cleaved by proteases within the endosomal/lysosomal compartment, leaving behind a small fragment called the class II-associated invariant chain peptide (CLIP) that occupies the peptide binding groove of the MHC class II molecule.
4. CLIP is then exchanged for antigenic peptides derived from extracellular pathogens, a process facilitated by the MHC class II-like molecule, HLA-DM.
5. The invariant chain plays a critical role in ensuring that MHC class II molecules present only foreign peptides to CD4+ T cells, thus promoting the initiation of an adaptive immune response against invading pathogens.

Review Questions

• Describe the function of the invariant chain in the assembly and trafficking of MHC class II molecules.
  • The invariant chain associates with newly synthesized MHC class II molecules in the endoplasmic reticulum, preventing the binding of self-peptides and directing the complex to specialized endocytic compartments. Within these compartments, the invariant chain is cleaved, leaving behind a small fragment called CLIP that occupies the peptide binding groove of the MHC class II molecule. This process ensures that MHC class II molecules only present foreign peptides derived from extracellular pathogens to CD4+ T cells, thereby promoting the initiation of an adaptive immune response.
• Explain the role of the invariant chain in the antigen presentation process mediated by MHC class II molecules.
  • The invariant chain plays a crucial role in the antigen presentation process by MHC class II molecules. It guides the MHC class II-invariant chain complex to specialized endocytic compartments where antigenic peptides are loaded onto the MHC class II molecules. The invariant chain is then cleaved, leaving behind the CLIP fragment that occupies the peptide binding groove. This CLIP fragment is then exchanged for foreign peptides derived from extracellular pathogens, a process facilitated by the MHC class II-like molecule, HLA-DM. This ensures that MHC class II molecules only present foreign peptides to CD4+ T cells, initiating an adaptive immune response against invading pathogens.
• Analyze the significance of the invariant chain in the context of the major histocompatibility complex and antigen-presenting cells.
  • The invariant chain is essential for the proper functioning of antigen-presenting cells, such as dendritic cells and macrophages, in the immune system. By associating with newly synthesized MHC class II molecules and guiding them to specialized endocytic compartments, the invariant chain ensures that MHC class II molecules only present foreign peptides derived from extracellular pathogens. This process is crucial for the initiation of an adaptive immune response, as it allows CD4+ T cells to recognize and respond to invading pathogens. Without the invariant chain, MHC class II molecules would be unable to effectively present foreign peptides, compromising the ability of the immune system to mount an effective response against infections. Therefore, the invariant chain is a critical component of the major histocompatibility complex and the antigen presentation process mediated by antigen-presenting cells.

Related terms

MHC Class II: MHC class II molecules are cell surface receptors that present peptide antigens to CD4+ T cells, initiating an adaptive immune response.

Antigen Presentation:

The process by which antigen-presenting cells, such as dendritic cells and macrophages, display foreign antigens on their surface for recognition by T cells.

Peptide Binding Groove: The specialized region within MHC class II molecules that binds and presents peptide fragments derived from extracellular pathogens.