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Major Histocompatibility Complex class II (MHC II) molecules presenting carrier-protein–derived peptides are essential mediators of the T-cell dependent immune response, particularly in the context of conjugate vaccines. These vaccines link a poorly immunogenic polysaccharide to a carrier protein, such as CRM197 or tetanus toxoid. Once internalized by B cells or other antigen-presenting cells, the carrier protein is proteolytically processed into peptides that are loaded onto MHC II molecules for surface display (Pollard et al., 2009). This peptide-MHC II complex is then recognized by the T-cell receptor (TCR) of CD4+ T-helper cells. This interaction provides the 'second signal' necessary for B cells to undergo affinity maturation and differentiate into long-lived memory B cells and plasma cells (Avci et al., 2011). Consequently, this target is fundamental to the efficacy of vaccines protecting against encapsulated bacteria like Streptococcus pneumoniae and Haemophilus influenzae type b.
The complex acts as a ligand for CD4+ T-cell receptors (TCRs). Recognition of the carrier-derived peptide presented by MHC II on B cells by cognate T-helper cells triggers the release of cytokines and CD40L-CD40 signaling, which drives B-cell proliferation, class-switch recombination, and memory B-cell differentiation (Pollard et al., 2009; Avci et al., 2011).
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