CRM197 carrier protein–derived peptides presented on MHC class II (CRM197-MHC II)

CRM197 is a non-toxic mutant of the diphtheria toxin, characterized by a single amino acid substitution (Gly52Glu) that abolishes its toxic ADP-ribosyltransferase activity while maintaining its structural integrity and immunogenicity (Bröker et al., 2011, Biologicals). In the field of vaccinology, CRM197 is widely utilized as a carrier protein for conjugate vaccines, where it is covalently linked to poorly immunogenic antigens such as bacterial polysaccharides. Upon administration, these conjugates are internalized by antigen-presenting cells (APCs) and B cells, where the CRM197 protein is proteolytically processed into peptides that are subsequently loaded onto Major Histocompatibility Complex (MHC) class II molecules (Pichichero, 2013, Human Vaccines & Immunotherapeutics). The presentation of these CRM197-derived peptides on MHC II allows for the recruitment and activation of CD4+ T helper cells through their T-cell receptors (TCRs). This interaction is critical for inducing a T-cell-dependent immune response, which enables B-cell isotype switching, affinity maturation, and the generation of long-lasting memory B cells against the target antigen (Shiny et al., 2016, Vaccine). This mechanism underpins the efficacy of several major vaccines, including those for Streptococcus pneumoniae and Neisseria meningitidis (PubMed, PMID: 21741490). Furthermore, the pre-existing immunity to CRM197 in many populations due to routine diphtheria vaccination can either enhance or, in some cases, suppress the response to new CRM197-conjugated vaccines. Understanding the specific peptides presented on MHC II is vital for optimizing vaccine design and predicting population-wide immune responses.

Other names

CRM197 T-cell epitopesCross-reacting material 197 peptidesDiphtheria toxin CRM197 mutant peptidesCRM197-derived MHC II ligandsCRM197 carrier protein

Activation of CD4+ T helper cells via TCR recognition of peptide-MHC II complexes to facilitate B-cell maturation and antibody production.