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Quantification of adaptive immune responses against protein binding interfaces in the streptococcal M1 protein

Type Information
Nr 85 (Research article)
Authors Torres-Sangiao, E; Happonen, L; Heusel, M; Palm, F; Gueto-Tettay, C; Malmström, Lars; Shannon, O; Malmström, Johan
Title Quantification of adaptive immune responses against protein binding interfaces in the streptococcal M1 protein
Journal Mol Cell Proteomics (2024) 2024 Mar 23 100753
DOI 10.1016/j.mcpro.2024.100753
Citations 0 citations (journal impact: 7.0)
Abstract Bacterial or viral antigens can contain subdominant protein regions that elicit weak antibody responses upon vaccination or infection although there is accumulating evidence that antibody responses against subdominant regions can enhance the protective immune response. One proposed mechanism for subdominant protein regions is binding of host proteins that prevent antibody production against epitopes hidden within the protein binding interfaces. Here, we used affinity-purification combined with quantitative mass spectrometry (AP-MS) to examine the level of competition between antigen-specific antibodies and host-pathogen protein interaction networks using the M1 protein from Streptococcus pyogenes as a model system. As most humans have circulating antibodies against the M1 protein, we first used AP-MS to show that the M1 protein interspecies protein network formed with human plasma proteins is largely conserved in naïve mice. Immunizing mice with the M1 protein generated a time-dependent increase of anti-M1 antibodies. AP-MS analysis comparing the composition of the M1-plasma protein network from naïve and immunized mice showed a significant enrichment of 292 IgG peptides associated with 56 IgG chains in the immune mice. Despite the significant increase of bound IgGs, the levels of interacting plasma proteins were not significantly reduced in the immune mice. The results indicate that the antigen-specific polyclonal IgG against the M1 protein primarily targets epitopes outside the other plasma protein binding interfaces. In conclusion, this study demonstrates that AP-MS is a promising strategy to determine the relationship between antigen-specific antibodies and host-pathogen interaction networks that could be used to define subdominant protein regions of relevance for vaccine development.