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To break the title down into parts:

  • There exist serology tests that detect the amount of an antibody (Ab) against a specific pathogen/antigen.

  • Every human produces their own Ab for a specific antigen by (relatively) random combination of different gene segments in their B cells, until one that recognizes the pathogen is found and produced in massive amounts.

  • One portion of every Ab is constant, whereas the portion that recognizes the antigen is variable. Even for antibodies (in different humans) that recognize the same antigen, albeit to a lesser degree.

What exactly does an antibody titer/serology test detect in the blood so that it can accurately measure the amount of antibodies against a specific antigen? I am assuming they use antibodies against the antigen-binding/variable portion of an antibody. But if the variable region differs from person to person, how can a universal antibody (to be used in serology tests) against it be generated?

Is the variable region not that variable, so that any lab-generated antibody against any functional antibody against a virus works well enough for an accurate measurement of antibodies against that virus? But even so the concept sounds hard to believe since even a single antigen can have multiple epitopes, and one person might have an Ab for epitope 1 of antigen X, while the other would have an Ab for epitope 2 of antigen X. And they would still be immune to the same virus, while a universal Ab titer test for the virus would be unable to detect antibodies from one of them.

Do they perhaps employ multiple lab-generated antibodies against most of the possible variations of human-generated antibodies in the tests?

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Specific antibodies are typically detected using ELISA.

The way you make a test for an antibody to a particular pathogen is not by using secondary antibodies to the specific part of the target antibody, but by using the antigen.

Different kits work differently, but the general idea is that you have antigen stuck to a surface, you put the sample on that surface. If there are antibodies to the antigen, they stick to it. Then you wash everything away and add a tagged antibody that binds to generic human antibodies.

See also https://www.sciencemag.org/news/2020/03/new-blood-tests-antibodies-could-show-true-scale-coronavirus-pandemic

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    $\begingroup$ ohh, using an antigen-coated surface makes a whole lot more sense. I don't know why I had such an extreme roundabout way of thinking. $\endgroup$ – Esoppant Mar 21 at 23:19

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