T cells familiar with coronavirus were found not only in those who had recovered

  Scientists compared the immune response to coronavirus in people who were sick and not sick with COVID-19 and found that the T cells of th...

 

Scientists compared the immune response to coronavirus in people who were sick and not sick with COVID-19 and found that the T cells of the latter also often recognize the virus, but they do not have antibodies to it. This lends support to the idea that the body may well be able to fight off the virus with a single T-cell response, either newly acquired or learned from old seasonal coronaviruses. In addition, scientists were able to determine the areas of coronavirus proteins to which T cells respond most often, and the corresponding popular variants of T-cell receptors. The results of this work, published in the journal  Immunity,  may be useful in the development of commercial tests to assess the T-cell response to SARS-CoV-2.

The fact that the T-cell response in COVID-19 plays an important role has been known since spring. This is supported by the lack of a positive correlation between low antibody levels and disease severity; in addition, in some patients, antibodies to SARS-CoV-2 cannot be found at all. In these cases, a person can cope with the virus at the expense of another part of the immune system - T cells. During the course of the disease, they learn to recognize the pathogen, destroy diseased cells on their own, and guide other participants in the immune response.

If a person, whose immune system was protected from the virus by T-cells, had the infection asymptomatically and did not pass the PCR tests on time, then it will not be possible to understand whether he really got sick with an antibody test. In this case, it is necessary to check the T-cell response, but so far this method of diagnosis is not widespread and commercial tests are just beginning to appear.

In the laboratory, T cell activity in response to pathogen recognition is measured using ELISPOT technology. When activated, T cells begin to secrete cytokines, and these cytokines can be “caught” using standard laboratory antibodies. The cytokine-antibody complexes are counted and therefore it is assessed whether the sample contains T cells recognizing a particular part of the virus.

To understand the immune response in more detail, a group of researchers from the National Medical Research Center of Hematology, led by Grigory Efimov, tested the antibody and T-cell responses to coronavirus proteins on three types of samples. The first samples were received in the spring from 34 COVID-19 patients, the second was collected at the same time from 7 who were not sick, and the third group of samples (10 plasma samples and 10  blood cells ) were taken from the 2017 and 2019 collections. 

It turned out that the majority of those who had been ill have both antibodies to all three tested coronavirus proteins and virus-specific killer T cells and T helper cells - two types of T cells. But in some of the patients, the answer was incomplete: in a couple of people, they did not find the necessary antibodies at all, while other patients did not have any of the types of T cells.

If we compare the results between the sick and not sick, we can see that in the latter, antibodies can be detected only in significantly smaller quantities - and, basically, to the most conservative N protein. At the same time, many samples contain T cells that can "turn on" when interacting with the details of SARS-CoV-2, and there are many more such samples in 2020. 

According to the first author of the article, Alina Shomuradova, the nature of such a response may be different: “The T-cell response can be observed due to the fact that immunological memory cells are activated for other coronaviruses that existed around us before 2019. Or, for example, these people actually suffered from COVID-19 asymptomatically and did not develop antibodies to the virus. " The presence of antibodies to the conserved N-protein can also be explained by the similarity between this protein in SARS-CoV-2 and other coronaviruses.

Antibody levels to three SARS-CoV-2 proteins in three groups of samples

Shomuradova et al. / Immunity

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Levels of the indicator of activation of T-killers (CD8 +) and T-helpers (CD4 +) interferon-gamma in three groups of samples

Shomuradova et al. / Immunity

A preprint of this work appeared back in May, and over the summer many other researchers independently came to the conclusion that a significant proportion of people with negative PCR tests, antibody tests, and no symptoms have T cells that can activate when they encounter SARS. CoV-2. For the correct diagnosis of such people, it is necessary to understand which parts of the coronavirus T-cells recognize most often and create commercial tests on their basis. To attack a pathogen, a T cell must first see its details on the  HLA receptors of the affected cell, and then also recognize it using its receptor (TCR). Not all sections of coronavirus proteins are suitable for this.

The researchers selected 13 epitope regions of the coronavirus S-protein, recognized by the most common European variant of the HLA-A receptor, and checked whether T cells from those who had recovered could recognize them. This variant of HLA was found in 17 patients, and in 16 of the T cells were "sharpened" for only two epitopes. These epitopes are found only in SARS-CoV-2, and the reaction to them can be used to recognize new patients who have trained their T cells on SARS-CoV-2, and not on its predecessors.

The comparative number of cells recognizing each of the 13 coronavirus epitopes in different donors

Shomuradova et al. / Immunity

Because T cells recognize the same epitope, it does not follow that they have the same recognition sequences on their receptors. However, using sequencing, the researchers found that for each of the two epitopes, the TCR sequences that recognize them are indeed similar or even identical between patients. In the future, these sequences can also be adapted for diagnostics. In non-sick people, the immune response to these two epitopes was minimal, which is consistent with the hypothesis that they trained their T cells on the predecessors of SARS-CoV-2, which do not have these epitopes.

Many of the coronavirus vaccines are specifically designed to include not only the antibody but also the T-cell response. These include the three leading vaccines currently competing for efficacy: vaccines from Pfizer, Moderna, and the Gamaleya Center.

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Corona Virus Magazine | Healthcare: T cells familiar with coronavirus were found not only in those who had recovered
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