CD8 subunit | Elisa - Clia - Antibody - Protein

Background

The CD8 molecule is a critical component of the immune system, primarily expressed on cytotoxic T cells (CTLs), which play a pivotal role in the immune response by targeting and destroying infected or malignant cells. CD8 exists as a dimer on the cell surface, typically composed of either two alpha chains (CD8αα) or a combination of an alpha and a beta chain (CD8αβ). The primary function of CD8 is to enhance the interaction between the T cell receptor (TCR) and the major histocompatibility complex (MHC) class I molecules on antigen-presenting cells, thereby facilitating the recognition of antigenic peptides and subsequent T cell activation.

Protein Structure

The CD8 molecule is a type I transmembrane glycoprotein with a well-defined structure that is crucial for its function in immune surveillance and response:

• Extracellular Domain:

The extracellular portion of CD8 consists of approximately 180 amino acids.

It includes an immunoglobulin-like domain, which is essential for binding to MHC class I molecules.

The CD8α and CD8β chains each have distinct extracellular regions that contribute to the molecule's binding specificity and stability.

• Transmembrane Domain:

This domain is composed of about 25 hydrophobic amino acids, allowing the CD8 molecule to anchor securely in the cell membrane.

The transmembrane region facilitates dimerization, which is crucial for the molecule's functional conformation and signaling capacity.

• Cytoplasmic Tail:

The cytoplasmic domain of CD8 is relatively short, comprising around 30 amino acids.

This region is involved in intracellular signaling pathways that are triggered upon antigen recognition.

It interacts with tyrosine kinases such as Lck, which are critical for signal transduction in T cells.

Classification and Subtypes

CD8 can exist in different forms based on its subunit composition:

CD8αα:

• This homodimer is found primarily on intestinal intraepithelial lymphocytes and some subsets of T cells.
• It plays a role in non-conventional immune responses and has been associated with regulatory functions.

CD8αβ:

• This heterodimer is the predominant form found on most cytotoxic T lymphocytes.
• It is essential for the conventional cytotoxic function of CTLs, enhancing the interaction with MHC class I molecules and facilitating effective immune responses against intracellular pathogens and tumor cells.

Function and Biological Significance

CD8 molecules perform several critical functions in the immune system:

Enhancement of TCR-MHC Interaction:

• CD8 binds to the alpha-3 domain of MHC class I molecules, stabilizing the interaction between the TCR and the MHC-peptide complex.
• This binding lowers the threshold for T cell activation, allowing for a more robust and efficient immune response.

Cytotoxic Activity:

• CD8+ T cells, upon activation, can directly kill infected or malignant cells through the release of cytotoxic granules containing perforin and granzymes.
• These cytotoxic granules induce apoptosis in the target cells, eliminating the source of infection or malignancy.

Regulation of Immune Responses:

• CD8+ T cells also produce various cytokines, such as interferon-gamma (IFN-γ), which enhance the immune response by activating other immune cells and promoting inflammation.
• They play a role in the immune memory, ensuring rapid and effective responses upon subsequent exposures to the same antigen.

Clinical Issues

CD8 expression and function are implicated in various clinical contexts:

Infections:

• The presence and activity of CD8+ T cells are crucial for the clearance of viral infections, such as HIV, hepatitis, and influenza.
• The effectiveness of CD8+ T cell responses often determines the outcome of these infections, with robust responses leading to viral clearance and weak responses associated with chronic infection.

Cancer:

• CD8+ T cells are essential for the immune surveillance and elimination of tumor cells.
• Immunotherapies, such as checkpoint inhibitors, aim to enhance the function of CD8+ T cells to improve anti-tumor responses.
• The presence of tumor-infiltrating CD8+ T cells is often associated with better prognosis in various cancers.

Autoimmune Diseases:

• Dysregulation of CD8+ T cell activity can contribute to the development of autoimmune diseases, where the immune system attacks healthy tissues.
• Conditions such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis have been linked to aberrant CD8+ T cell responses.

Transplantation:

• In the context of organ transplantation, CD8+ T cells can mediate graft rejection by recognizing and attacking the foreign tissue.
• Immunosuppressive therapies aim to mitigate CD8+ T cell responses to promote graft tolerance and prevent rejection.

Summary

The CD8 molecule is a vital component of the immune system, primarily found on cytotoxic T lymphocytes. Its structure, comprising an extracellular immunoglobulin-like domain, a transmembrane region, and a cytoplasmic tail, is crucial for its role in enhancing TCR-MHC interactions and facilitating immune responses. CD8 exists in different forms, with the CD8αβ heterodimer being predominant on CTLs and essential for conventional cytotoxic activity. CD8+ T cells are involved in various functions, including direct cytotoxicity, cytokine production, and immune regulation. Clinically, CD8 is significant in infections, cancer, autoimmune diseases, and transplantation. Understanding the role of CD8 in these contexts is crucial for developing therapeutic strategies to modulate immune responses effectively.