The immune system relies on the precise identification of cellular threats, a process carried out by specialized cells. One such cell, the cytotoxic T lymphocyte, surveys the body for cells that have become infected by viruses or have turned cancerous. To perform this function, it uses surface proteins to inspect other cells, including the CD8 co-receptor, which plays a direct part in this recognition process.
The ability of a cytotoxic T lymphocyte to eliminate a compromised cell depends on its capacity to correctly identify it as a threat. The molecular structure of the CD8 protein is intrinsically linked to this function. Understanding its architecture reveals how these immune cells are guided to their targets, allowing the T cell to confirm it has found an infected or malignant cell and initiate a response to destroy it.
Core Composition of the CD8 Molecule
The CD8 molecule, embedded in the outer membrane of cytotoxic T cells, is a glycoprotein, meaning it is a protein with attached sugar molecules, or glycans. These carbohydrates contribute to the molecule’s stability and function. The complete CD8 structure is not a single protein chain but a dimer, a complex formed by two separate protein chains linked together.
There are two distinct types of chains that can construct the dimer: the CD8α (alpha) chain and the CD8β (beta) chain. Each chain is encoded by a separate gene and has a unique amino acid sequence. While they share similarities in their overall organization, their differences allow for varied functions.
The most prevalent form of the CD8 co-receptor on cytotoxic T lymphocytes is a heterodimer, consisting of one CD8α chain paired with one CD8β chain. The two chains are held together by a disulfide bond, which forms between specific cysteine amino acids in each chain. This alpha-beta pairing is the most common configuration and is recognized for its efficient role in T cell activation.
Detailed Architecture: Domains of CD8
The CD8α and CD8β protein chains are folded into several distinct regions, or domains, each with a specific purpose. This modular organization allows different parts of the molecule to perform specialized tasks. Both chains are composed of an extracellular segment that projects from the cell, a transmembrane section that anchors it, and a cytoplasmic tail that reaches into the cell’s interior.
The portion extending furthest from the cell surface is the extracellular domain, which has a shape known as an immunoglobulin (Ig)-like fold. This stable, compact structure is also found in antibodies and gives this part of the protein the ability to interact with other molecules. The Ig-like domain is connected to the cell membrane by a flexible stalk called the hinge region, which provides spacing and allows the domain to orient itself correctly for binding.
Anchoring the entire CD8 molecule within the T cell’s membrane is the transmembrane domain. This segment consists of a stretch of hydrophobic amino acids that sit within the lipid-rich environment of the cell membrane, ensuring CD8 remains tethered to the cell surface.
Extending into the cytoplasm is the cytoplasmic tail. This short segment of amino acids serves as a docking site for intracellular signaling proteins. While it does not have enzymatic activity itself, its structure is designed to bind other molecules that carry messages inside the cell, translating an external event into an internal response.
Structural Basis for Cell Recognition
The primary function of the CD8 co-receptor is to assist the T cell receptor (TCR) in recognizing target cells. Nearly all nucleated cells in the body display fragments of their internal proteins on their surface using a molecule called the Major Histocompatibility Complex (MHC) Class I. If a cell is infected, it will display viral protein fragments on its MHC Class I molecules, signaling that it is compromised.
The CD8 molecule acts as a co-receptor by working alongside the TCR to engage the same MHC Class I molecule. While the TCR inspects the peptide fragment presented by MHC, the Ig-like domain of the CD8α chain binds to a non-variable region of the MHC Class I molecule itself. This interaction is a precise structural fit between the flexible loops on the CD8 domain and a corresponding loop on the MHC protein.
This binding event stabilizes the entire complex, holding the T cell and the target cell together. This adhesion allows the TCR more time to properly engage with the peptide-MHC complex. This stabilization enhances the overall sensitivity of the T cell, ensuring it can be triggered even by low numbers of foreign peptides on a target cell’s surface.
CD8 Variations and Signaling Connections
While the CD8αβ heterodimer is the most common form, a variation consisting of two identical CD8α chains, a CD8αα homodimer, also exists. This homodimer is present on different immune cell types, including some natural killer (NK) cells and intraepithelial lymphocytes. The structure of the CD8αα homodimer allows it to interact with a different set of molecules, suggesting it performs distinct regulatory functions.
The translation of cell recognition into an internal action is mediated by the cytoplasmic tail of the CD8α chain. The amino acid sequence of this tail creates a binding site for an enzyme inside the T cell called Lymphocyte-specific protein tyrosine kinase (Lck). This kinase is a signaling protein that remains associated with the CD8 co-receptor.
When CD8 and the TCR successfully bind to an MHC Class I molecule, the Lck enzyme is brought into close proximity with the TCR complex. This proximity is the trigger for T cell activation. The recruited Lck adds phosphate groups to components of the nearby TCR complex, starting a signaling cascade that culminates in the activation of the cytotoxic T cell, which then releases molecules that cause the target cell to self-destruct.