CD4+ T-cell receptor recognizing CRM197-derived peptide–MHC II complexes

CD4+ T-cell receptors (TCRs) recognizing CRM197-derived peptide–MHC II complexes are essential mediators of the immune response to conjugate vaccines. CRM197, a non-toxic mutant of the diphtheria toxin, acts as a carrier protein that is processed by antigen-presenting cells to display specific peptides on MHC Class II molecules (Bottrel et al., 2020, Frontiers in Immunology). The recognition of these complexes by CD4+ T-cells triggers the activation of helper T-cell pathways, which are crucial for inducing B-cell isotype switching and memory B-cell formation against conjugated polysaccharides (Avci et al., 2011, Nature Medicine). This interaction is the fundamental basis for the efficacy of vaccines against pathogens like Streptococcus pneumoniae and Neisseria meningitidis in populations with immature immune systems (Shinefield, 2010, Vaccine). Because CRM197 is a single protein, the diversity of the TCR repertoire and the specific HLA alleles of the individual significantly influence the strength and breadth of the resulting immune protection (Malito et al., 2012, PNAS). Monitoring the activation of these specific CD4+ T-cells serves as a biomarker for vaccine immunogenicity and helps in the design of next-generation carrier proteins.

Other names

CRM197-specific T-cell receptorCRM197-reactive CD4+ TCRDiphtheria toxoid-specific TCRCRM197-peptide-MHC II complex receptor

Activation of CD4+ T-helper cells through the recognition of CRM197-derived peptides presented on MHC Class II molecules, facilitating B-cell help and antibody production (Avci et al., 2011, Nature Medicine).