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SARS-CoV-2 mutations affect antigen processing by the proteasome to alter CD8+ T cell responses

Dannielle Wellington1,2, Zixi Yin1,2, Zhanru Yu1,3

  • 1Chinese Academy of Medical Sciences (CAMS) Oxford Institute, Nuffield Department of Medicine, Oxford University, Oxford, OX3 7FZ, UK.

Heliyon
|October 16, 2023
PubMed

Insights

SARS-CoV-2 mutations near viral epitopes impact T cell responses. Some mutations cause immune escape, while others enhance T cell activation, offering insights for vaccine development.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Viral mutations can lead to immune escape from T cells.
  • The role of mutations in regions flanking SARS-CoV-2 epitopes is largely unknown.

Purpose of the Study:

  • To investigate how mutations in flanking regions of SARS-CoV-2 nucleoprotein CD8+ T cell epitopes affect proteasomal processing and T cell activation.
  • To understand the mechanisms of immune escape and potential enhancement mediated by these mutations.

Main Methods:

  • Analysis of two SARS-CoV-2 nucleoprotein CD8+ T cell epitopes.
  • Assessment of proteasomal processing efficiency for epitope production.
  • Measurement of CD8+ T cell responses to mutated epitopes.

Main Results:

  • The NP-Q7K mutation within an epitope region decreased T cell responses, suggesting immune escape due to impaired proteasomal processing.
  • Flanking mutations (NP-P6L and NP-D103N/Y) enhanced CD8+ T cell responses by improving epitope production via the proteasome.
  • Mutations outside the core epitope sequence significantly influence proteasomal processing.

Conclusions:

  • SARS-CoV-2 mutations in flanking regions can modulate T cell immunity.
  • These mutations can either promote immune escape or enhance T cell activation.
  • Understanding these effects is crucial for designing effective vaccines against SARS-CoV-2.

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