Major histocompatibility complex class II molecules presenting CRM197-derived peptides (MHC II-CRM197 complex)

MHC class II molecules presenting CRM197-derived peptides are specialized immunological complexes essential for the efficacy of conjugate vaccines. CRM197 is a non-toxic mutant of the diphtheria toxin, containing a single amino acid substitution (G52E), which serves as a potent carrier protein for polysaccharide antigens (Bröker et al., 2011, Biologicals). In the immune system, antigen-presenting cells (APCs) like B cells internalize the CRM197-polysaccharide conjugate, process the protein component into peptides, and display these peptides on MHC class II molecules (Avci et al., 2011, Nature Medicine). This specific peptide-MHC II complex is then recognized by the T-cell receptors (TCRs) of CD4+ helper T cells. These T cells provide the necessary signals, such as cytokines and CD40L, for B-cell maturation and isotype switching. This process leads to the formation of high-affinity memory B cells and long-lived plasma cells. This mechanism effectively converts T-cell independent responses into T-cell dependent ones, providing long-term protection against pathogens like Streptococcus pneumoniae (Pichichero, 2013, Human Vaccines & Immunotherapeutics). Drugs interacting with this target include major conjugate vaccines such as Prevnar 13 and Menveo, which rely on the formation of these complexes to elicit a robust immune response.

Other names

MHC II-CRM197HLA-DR-CRM197 peptide complexCRM197-peptide-MHC II complexCross-reacting material 197-MHC II complex

The mechanism involves the proteolytic processing of the CRM197 carrier protein within antigen-presenting cells, followed by the loading of resulting peptides into the peptide-binding groove of MHC class II molecules. These complexes are then transported to the cell surface where they serve as the primary ligand for CRM197-specific CD4+ T-cell receptors, triggering T-cell help for B-cell antibody production (Avci et al., 2011, Nature Medicine).