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Helper T-cell receptors (TCRs) recognizing CRM197-derived peptide-MHC II complexes are essential mediators of the immune response to conjugate vaccines using CRM197 as a carrier protein (Pichichero, 2013). CRM197 is a genetically detoxified version of the diphtheria toxin, containing a single amino acid substitution (Gly52Glu) that renders it non-toxic while maintaining its immunogenicity (Bröker et al., 2011). In the context of vaccination, antigen-presenting cells (APCs) internalize the CRM197-conjugate, process the protein into peptides, and present them via MHC class II molecules to CD4+ T-cells (Avci et al., 2011). The engagement of specific TCRs with these peptide-MHC II complexes triggers T-cell proliferation and the release of cytokines, which are necessary for B-cell activation and memory formation (Pace, 2013). This mechanism allows non-immunogenic polysaccharides to elicit a T-cell dependent immune response, leading to high-affinity antibody production (Pichichero, 2013). These TCRs are therefore indirect targets for a wide range of conjugate vaccines targeting pathogens like Streptococcus pneumoniae and Neisseria meningitidis.
Activation of CD4+ helper T-cells through TCR recognition of CRM197 peptides presented on MHC class II molecules, facilitating B-cell isotype switching and memory formation for conjugated antigens.
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