CD8+ T Cell and Covid-19 Variants

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Recently, the US National Institute of Allergy and Infectious Diseases (NIAID) has found that the CD8+ T cell of the human immune response has remained active against the new variants of Covid-19.

About the CD8+ T Cell

• These are also called cytotoxic T lymphocytes, or CTLs and like CD4+ Helper T cells, are generated in the thymus and express the T-cell receptor.
  • The thymus is a lymphoid gland composed of two identically sized lobes, located behind the sternum (breastbone) but in front of the heart.
  • It filters and monitors blood content and produces the white blood cells called T-lymphocytes.
• These are very important for immune defence against intracellular pathogens, including viruses and bacteria, and for tumour surveillance.
• When a CD8+ T cell recognises its antigen and becomes activated, it has three major mechanisms to kill infected or malignant cells.
  • The first is secretion of cytokines, primarily TNF-α and IFN-γ, which have antitumor and anti-viral microbial effects.
  • The second major function is the production and release of cytotoxic granules, which contain two families of proteins namely perforin and granzymes.
    • Perforin forms a pore in the membrane of the target cell which allows the granzymes to enter the infected or malignant cell.
    • Granzymes sever the proteins inside the cell, shutting down the production of viral proteins and ultimately resulting in apoptosis (programmed cell death) of the target cell.
    • CD8+ T cells are able to release their granules, kill an infected cell, then move to a new target and kill again, often referred to as serial killing.
  • The third major function of CD8+ T cell destruction of infected cells is via Fas/FasL interactions.
    • Activated CD8+ T cells express Fas ligand (FasL, a type II membrane protein which can induce apoptotic cell death) on the cell surface, which binds to its receptor, Fas, on the surface of the target cell.
    • This binding results in the activation of the caspase cascade, which results in apoptosis of the target cell.

About the Research

• The scientists investigated whether CD8+ T cells in the blood of recovered Covid-19 patients, infected with the initial virus, could still recognise the Covid-19 variants, namely
  • United Kingdom Variant (B.1.1.7)
  • South African Variant (B.1.351)
  • Brazil Variant (B.1.1.248)
• Each of these variants has mutations throughout the virus, and mainly in the region of spike protein that the virus uses to attach to and enter human cells.
• Scientists thought that mutations in this spike protein region could make it less recognisable to T cells and neutralising antibodies, which are made by the immune system’s B cells following infection or vaccination.

Key Findings

• In their study of recovered Covid-19 patients, the researchers determined that Covid-19 specific CD8+ T cell responses remained largely intact and could recognise virtually all mutations in the variants studied.
• Although more studies and research is needed, the researchers note that the T cell response in convalescent individuals, and most likely in vaccine recipients, are largely not affected by the mutations found in these three variants, and should offer protection against emerging variants.
• Optimal immunity to Covid-19 likely requires strong multivalent T-cell responses in addition to neutralising antibodies and other responses to protect against current and emerging strains.
• They have also emphasised on the importance of monitoring the breadth, magnitude and durability of the anti-Covid-19 T-cell responses in recovered and vaccinated individuals as part of any assessment to determine if booster vaccinations are needed.

Source: IE