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I am curious whether there are structural correlates in antibodies that relate not to epitope sequence but to epitope size. Specifically, I imagine that the antibody-epitope interface size is constrained to some extent by the structure of the variable regions that confer specificity, which likely do not have any direct interaction with the epitope.

Put another way, taking this illustration below from this educational site, it seems to me that the $V_{H}$ and $V_{L}$ portions (including hypervariable regions) that are not necessarily part of the orange "hand" interacting with the antigen, but rather lead to the gross shape of this "hand", can significantly affect the size of the epitope independently of the epitope linear sequence (assuming a linear epitope).

Illustration of antibody structure, indicating antigen interaction in variable region as an orange hand

I'm aware that epitope prediction is an extremely difficult computational task, so presumably there is not a straightforward structural encoding of epitope size. Nonetheless, I'm curious if anything is known.

I found this question pointing to a paper that indicates substantial variation in the size of the epitope, leading me to believe that such an epitope size-antibody conformation relationship might be possible. This possibly suspect company page indicates some very small possible epitope of 5 amino acids or less, which would suggest a high degree of constraint in the interface if true.

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  • $\begingroup$ Slightly OT, but why do you think that page is "possibly suspect"? $\endgroup$
    – MattDMo
    Jan 23, 2023 at 17:56
  • $\begingroup$ @MattDMo It's a marketing page without supporting data, i.e. "trust us". I don't personally doubt that it's more or less true, but I've noticed that SE Biology tends to be pretty critical of such sources. $\endgroup$ Jan 23, 2023 at 18:45
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    $\begingroup$ I agree. I used to work at an antibody company, and we had tons of internal data that we'd never release, because it's proprietary and gave us a business advantage. No so good for an open-access site like this, but good for the customers who believed the marketing (which was for the most part rather accurate, I must say). $\endgroup$
    – MattDMo
    Jan 23, 2023 at 19:20

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