Abstract
ABSTRACTB cell epitopes must be solvent accessible for recognition by cognate B cells and antibodies. Here, we sought to study such premise for B cell epitopes targeted during infection in humans, available at the Immune Epitope Database. Most of these B cell epitopes were virus-specific linear B cell epitopes and so we focused on them, analyzing first the localization of the relevant antigens. Antigen localization could be unequivocally assigned to 26498 linear B cell epitopes. Of those, 18832 B cell epitopes belonged to antigens that remain enclosed in host cells and/or virus particles, hidden to antibody recognition, while just 7666 lie in ectodomains of viral envelope antigens and/or mature secreted antigens, visible to antibody recognition. Next, we selected B cell epitopes that mapped in antigens with known tertiary (3D-)structures and determined residue relative solvent accessibility (rRSA), comparing them with those of conformational B cell epitopes obtained from available 3D-structures of antigen-antibody complexes. rRSA values computed form linear B cell epitopes had a median value of 23.00%, while that of conformational B cell epitopes was 48.50%. Moreover, considering average rRSA values per entire epitopes (eRSA), only 32.72% of the linear B cell epitopes had eRSA values minimally comparable to those of conformational B cell epitopes. In sum, our results point that most virus-specific B cell epitopes targeted during infection are unreachable to antibody recognition on intact viral particles and/or host cells. Hence, we must conclude that antigen recognition by antibodies must be preceded by degradation/processing of viral particles and infected cells.
Publisher
Cold Spring Harbor Laboratory
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