Other than antibodies, the immune response to coronavirus is complex

After all, the only way for society to return to its normal appearance after the current pandemic is to reach what is called herd immunity. This is where a significant proportion of the population has acquired immunity to SARS-CoV-2 either by infection or vaccine, and most people exposed to the virus already have it. I am. This means that the infection rate will decline and eventually disappear, protecting the whole society.

Given that this is our ultimate goal, we need to understand how the immune system responds to this virus. Most of what we know is based on a combination of what we know about other coronaviruses that infect humans and the antibody response to SARS-CoV-2. However, now we have data on T-cell responses, indicating that they are more complex: longer lasting, widespread, overlapping with responses to previous coronavirus infections. Including It remains unclear what this means for the long-term protection outlook.

What we know now

SARS-CoV-2 is one of seven coronaviruses known to infect humans. Some of these, like SARS and MERS, have just recently jumped into humans. More deadly than SARS-CoV-2, but fortunately it does not spread efficiently among humans. These viruses appear to trigger a long-lasting immune response after infection. This is in contrast to the four coronaviruses that circulate widely in humans causing cold-like symptoms. These viruses induce immunity that appears to last less than a year.

Little is known about the immune response to SARS-CoV-2. By tracking antibody production, it is clear that many infected people have a strong immune response, but “many” is far from “all.” There are many fluctuations At the level of response. Its variability Great difference in severity COVID-19 between patients. One of the concerns is the reaction of antibodies to SARS-CoV-2. Appears to be declining rapidly..

However, antibody responses are only part of the immune system’s defense against pathogens. Antibodies usually recognize proteins present on the surface of viruses. This is because the cells that make the antibody are exposed to the protein. However, there is another way of recognizing pathogens in a second group of cells called T cells. T cells are dependent on the system used by all cells. It takes small pieces of proteins made by T cells and presents them on the cell surface. Depending on how the system works, it may recognize more proteins made by the virus, not just those on the surface.

(Some immune cells that swallow pathogens also carry protein fragments on their surface.)

Upon reaching it, T cells that recognize these small pieces of protein as foreign can undergo a variety of reactions, from activating immune cells in their mates to killing the cells that make the foreign protein. Studying T cell responses is much more difficult because it is based on cells rather than antibodies that are proteins. But such studies are equally important for long-term immunity.

Studying Ts

To study T cell responses, a group of researchers based in Singapore focused on proteins that are internal to the virus or used only in infected cells, and thus are not the main focus of the antibody response. It was To confirm the response to these proteins, the researchers created a set of 15 amino acid long protein fragments that span the entire length of the protein. He then collected blood cells from those who had recovered from COVID-19, those who had recovered from the original SARS, and those who had never been exposed to either virus.

These fragments were pooled and mixed with blood cells to see if the T cells in them responded to them. By narrowing the pool, researchers were able to identify the specific fragment that the T cell was responding to, or the specific region of the protein from which it was derived. Responses were recorded by checking the levels of immune signaling molecules produced by T cells.

One potentially encouraging finding was that people who were exposed to the original SARS virus 17 years ago still had T cells that responded to fragments of the virus. This was true even though the antibody response to this virus generally declined after a few years. Not too surprisingly, those with COVID-19 recently also had T cells that respond to fragments of the viral protein.

However, there were salient features of the SARS and COVID-19 fragments that T cells responded to, and many of them were identical. SARS-CoV-1 and -2 are distinct viruses with different evolutionary histories, but many of their proteins are very similar. (It’s probably because they continue to perform similar functions, and thus there is evolutionary pressure to change.) As a result, some of the fragments created based on the SARS-CoV-2 protein Coincidentally, it was identical with a SARS equivalent protein-CoV-1. Therefore, T cells that recognize one of these fragments are able to recognize both viruses, even from patients with only one exposed.

surprise!

This sets the stage for the most amazing results of the study. Participants never exposed to either SARS virus also had some T cells that recognized fragments of the SARS-CoV-2 protein. This was not the case for all participants in the unexposed group. Only about half of them had these reactive T cells. But again, it was largely based on cells that responded to fragments of the same protein between SARS-CoV-2 and the common cold-causing virus.

Most, but not all. There were two exceptions to this, which did not look like cold viruses, but were two fragments of a protein that elicited a response from T cells of unexposed participants. Researchers have a hard time explaining them. Their only suggestion is that some other pathogens occur randomly and have a small section of protein that looks like this. There were also differences between the groups for any of the three proteins recognized by T cells, but the significance of these differences is unclear.

What does that mean?

So does this mean a common cold could potentially protect some of us from COVID-19? There is no way to know based on these results. Previous exposure to the cold-causing coronavirus appears to elicit a different response to the protein than exposure to SARS-CoV-2. Also, there are no signs that antibodies against common cold viruses cross-react with SARS-CoV-2. Is a T cell-based response alone sufficient to prevent the virus? I do not know.

At the same time, the fact that this response is only present in a subset of people who have never been exposed may explain some of the differences in severity of COVID-19 symptoms. There’s obviously a lot of work to do here.

The importance of T cell-based immunity is also important in understanding the apparently variable antibody response problem and the signs that it can be rapidly weakened once the SARS-CoV-2 infection is cleared. This study shows that T cell responses are consistently strong in this small population. Parallel work on SARS patients has shown that this response also lasts much longer than antibody-based immune responses. Therefore, one may be less worried about an irregular antibody response, if sufficient to provide protection from reinfection. Again, I don’t know yet.

This may also impact the development of vaccines that tend to focus on producing neutralizing antibodies.

All of this implicates a better understanding of T cell responses to SARS-CoV-2. This is a shame considering how difficult it is to study T cells.

Nature, 2020. DOI: 10.1038 / s41586-020-2550-z (About DOI).