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9 December, 2020 14:42

Russian Immunologists Identify Which Fragments of the SARS-CoV-2 Spike Protein Are Recognised by T Cells of Recovered Patients

Immunologists at the National Research Centre for Hematology have described regions of the SARS-CoV-2 spike protein. This protein is present in most coronavirus vaccines under development, and its regions trigger the most robust immune response in patients who recover from COVID-19. First of all, the scientists found that the number of T cells that recognize the virus is much higher in people who have never had COVID-19 and whose blood samples were collected in spring 2020 than those whose samples were collected prior to the pandemic. Second, they identified the specific regions of the spike protein that most often trigger a response in immune cells (T cells) of patients who recover from COVID-19. The investigation into the mechanisms of acquired immunity to SARS-CoV-2 is important for the continued development of coronavirus vaccines and methods for diagnosing herd immunity. The results of this work, which was supported by the Russian Science Foundation (RSF), were published in the prestigious journal Immunity (Cell Press).
Credit: cdc.gov

Scientists all over the world are studying the immunological processes associated with the novel SARS-CoV-2 infection. Most patients who recover from COVID-19 have antibodies to the virus but, in some patients, this type of immune response is completely absent. In such cases, T cells – another part of the immune system – could be responsible for eliminating the virus. T cells in most COVID-19 patients can, indeed, recognize virus fragments. But here is the surprising thing: some people who have never had COVID-19 also have T cells that respond to SARS-CoV-2. Researchers at the Centre for Haematology described both types of immune response (antibody- and T-cell-mediated) to the novel coronavirus in three groups of people: those who have recovered from COVID-19, those who never had the disease and those whose blood samples were collected before the pandemic and stored in a biobank.

The scientists analyzed the immune response to spike protein, which enables the virus to enter cells, so it is included in most vaccines being developed to fight SARS-CoV-2. After encountering the protein, the immune system “remembers” it and can neutralize it if it ever enters the body. First of all, it turned out that the number of T cells that recognize the virus is much higher in people who have never had COVID-19 and whose blood samples were collected in spring 2020 than in those whose samples were collected before the pandemic. Authors of the study offer the following explanation: some of those who never developed the disease were probably nevertheless exposed to the virus.

“We don't quite understand the nature of this immune response,” comments Alina Shomuradova, the first author of the article and an RSF grantee working at the National Medical Research Centre for Haematology. “T-cell response might be due to activation of immunological memory cells specific to other coronaviruses that were also around before 2019. Or these people, in fact, had subclinical COVID-19 but failed to produce antibodies to the virus.”

The most significant result of the work is the identification of the specific regions of spike protein most likely to trigger a response in the T cells of patients who recover from COVID-19. Two such regions are recognized by the immune systems of most carriers of the most prevalent variant of the HLA-A gene in Europe, which is responsible for the presentation of virus fragments by T cells. Both regions are specific to the novel SARS-CoV-2, i.e., they set it apart from other coronaviruses. This means that they can be used to identify people who have had COVID-19.

The authors also identified which specific T cell receptors recognize individual virus fragments. Thus, the study published by the Russian scientists provides information about viral protein regions that trigger an immune response in humans and about sequences of human immune cell receptors that bind specifically to these regions. This data is important for understanding the interaction between our immune system and SARS-CoV-2 at a fundamental level and for tackling practical problems of diagnosis and vaccination.

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