Mutant peptides derived from SARS-CoV-2 inhibit the ability of T cells to recognize and destroy infectious cells

An in-depth study of 747 SARS-CoV-2 virus has revealed that mutant peptides derived from the virus cannot effectively bind to inflammatory proteins on the surface of infectious cells and thus inhibit CD8 activation.⁺ killing T cells that recognize and destroy these infectious cells.

These peptides, the authors say, represent one way in which the coronavirus bypasses T killer cell responses and immune stymies in the host.

Their results may be particularly important for SARS-CoV-2 subunit vaccines, such as the currently used RNA vaccines, which stimulate responses against a limited number of viral peptides displayed on T cells; such vaccines may be at risk of stunted efficacy if any of these target peptides are contaminated in emerging viral changes.

However, because T cells can widely identify a wide range of epitopes, it remains to be determined just how mutations in single epitopes actually affect viral control. Killer T cells kill infectious cells when viral epitopes are identified, which are displayed on the surface of infectious cells according to major class I histocompatibility complex proteins (MHC-I), or human leukocyte antigen (HLA) proteins such as called in humans. Some roles in these epitopes are critical for the presentation of HLA-I, and mutations in these regions may impede epitope binding to the HLA.

Benedikt Agerer and colleagues identified mutations in T cell epitopes killed from SARS-CoV-2 after a deep 747 strain of SARS-CoV-2 virus. They demonstrated that these mutant peptides could not effectively bind to HLA proteins in a cell, without a cell, in vitro assay. When exposed to T kill cells isolated from HLA-matched COVID-19 patients, binding of mutant peptides to HLA-I reduced T cell proliferation, decreased production of inflammatory factors such as IFN-γ, and stopped the whole cell killing activity. of T killer cells. In future work, the authors aim to address how these “escape” mutations are maintained when they are transmitted between individuals with different HLA subtypes and how viruses are carrying epitope mutations affects the severity of infection.