Epitopes, paratopes, and other topes 30 years on: Understanding what we are talking about.

The question of which protein antigens, such as HLA class I or class II molecules, will bind, and how well, to a given antibody is often assumed to depend exclusively on the details of protein surface structure. These structures are usually based on static models resulting from X-ray crystallography. While these notions are useful, the ultimate causal factors determining how well a given antigen binds a given antibody are based in thermodynamics and can include atomic mobility and the time-varying conformations of proteins. In this article, fundamental biophysical principles of antibody-antigen interaction are discussed, concepts critical for a deeper understanding of the pertinent molecular phenomena are highlighted, and common misunderstandings are identified and debunked.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)