Percent of highly immunogenic amino acid residues forming B-cell epitopes is higher in homologous proteins encoded by GC-rich genes

We analyzed the dependence of the percent of highly immunogenic amino acid residues included in B-cell epitopes of homologous proteins on the GC-content (G+C) of genes coding for them in twenty-seven lineages of proteins (and subsequent genes), which belong to seven Varicello and five Simplex viruses. We found out that proteins encoded by genes of a high GC-content usually contain more targets for humoral immune response than their homologs encoded by GC-poor genes. This tendency is characteristic not only to the lineages of glycoproteins, which are the main targets for humoral immune response against Simplex and Varicello viruses, but also to the lineages of capsid proteins and even “housekeeping” enzymes. The percent of amino acids included in linear B-cell epitopes has been predicted for 324 proteins by BepiPred algorithm (www.cbs.dtu.dk/services/BepiPred), the percent of highly immunogenic amino acids included in discontinuous B-cell epitopes and the percent of exposed amino acid residues have been predicted by Epitopia algorithm (http://epitopia.tau.ac.il/). Immunological consequences of the directional mutational GC-pressure are mostly due to the decrease in the total usage of highly hydrophobic amino acids and due to the increase in proline and glycine levels of usage in proteins. The weaker the negative selection on amino acid substitutions caused by symmetric mutational pressure, the higher the slope of direct dependence of the percent of highly immunogenic amino acids included in B-cell epitopes on G+C.

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► Percent of highly immunogenic amino acids depends on G+C in 96% of cases.
► Percent of amino acids in linear B-cell epitopes depends on G+C in 92% of cases.
► Percent of exposed amino acids depends on G+C in 60% of cases.