From the first description of omicron, researchers were concerned about its variant of the SARS-CoV-2 virus. By going through the list of mutations it carried, scientists were able to identify a number that would likely make the variant more infectious. Other mutations were even more concerning, as they would likely interfere with the immune system’s ability to recognize the virus, which would put it at risk for those who had been vaccinated or had suffered from previous infections.
Buried within the subtext of those concerns, there was a clear implication: Scientists could simply look at the amino acid sequence in a coronavirus’ spike protein and get a feel for how the immune system would respond to it. .
This knowledge is based on years of studying how the immune system works, combined with a lot of specific information about its interactions with SARS-CoV-2. The following is a description of these interactions, along with their implications for viral evolution and present and future variants.
Ts and Bs
To understand the function of the immune system, it is easier to divide its responses into categories. For starters, there is the innate immune response, which tends to recognize the general characteristics of pathogens rather than the specific properties of individual bacteria or viruses. The innate response is not refined by vaccination or previous exposure to a virus, so it is not really relevant to the discussion of variants.
What interests us is the adaptive immune response, which recognizes the specific characteristics of pathogens and generates a memory that produces a rapid and robust response if the same pathogen is seen again. It is the adaptive immune response that we stimulate with vaccines.
Adaptive response can also be divided into categories. In terms of relevant immune responses, we care most about those mediated by antibody-producing B cells. The other important part of adaptive immunity, the T cell, uses a completely different mechanism to identify pathogens. We know much less about the T cell response to SARS-CoV-2, but more on that later. For now, we’ll focus on antibodies.
Antibodies are large assemblages (in molecular terms) of four proteins. Most proteins are the same in all antibodies, which allows immune cells to interact with them. But each of the four proteins has a variable region that is different in each B cell produced. Most of the variable regions are unnecessary, and others recognize the body’s own proteins and are eliminated. But by chance, some antibodies have variable regions that recognize a segment of a protein made by a pathogen.
The part of the pathogen’s protein that the antibody recognizes is called an epitope. Epitopes vary from protein to protein, but they share certain characteristics. They need to be outside the protein, rather than buried inside, for the antibody to hit it in the first place. And they often have polar or charged amino acids because these form stronger interactions with the antibody.
You can’t just look at the amino acids in an antibody and say what it’s going to bind to. But if you have sufficient amounts of a specific antibody, it’s possible to do what’s called “epitope mapping,” which involves determining precisely where on a protein the antibody binds. In some cases, this can include a specific list of amino acids that the antibody recognizes.
In general, having antibodies stuck to a pathogen in the bloodstream facilitates detection and elimination of the pathogen by specialized immune cells. For this function, it doesn’t matter where the antibody sticks. But there are also specific interactions that can inactivate a virus in some cases, as we will see below.