T-cell receptor (TCR) recognizing CRM197 or diphtheria toxoid peptides presented on MHC class II (TCR-CRM197/DT)

T-cell receptors (TCRs) recognizing CRM197 or diphtheria toxoid peptides presented on MHC class II are specialized immune receptors that play a pivotal role in the efficacy of conjugate vaccines. CRM197 is a genetically detoxified version of the diphtheria toxin (DT) that contains a single amino acid substitution (Gly52Glu), rendering it non-toxic while preserving its immunogenic T-cell epitopes (Pichichero, 2013, PMID: 23414368). These TCRs, located on the surface of CD4+ T helper cells, specifically bind to CRM197-derived peptides that have been processed and displayed by MHC class II molecules on antigen-presenting cells (APCs). This binding event initiates a signaling cascade that activates the T cell, leading to the secretion of cytokines and the expression of surface molecules like CD40L, which are essential for stimulating B cells to produce high-affinity antibodies against conjugated haptens or polysaccharides (Avci et al., 2011, PMID: 21785434). This mechanism, known as the carrier effect, is fundamental to the design of vaccines against encapsulated bacteria such as Streptococcus pneumoniae and Neisseria meningitidis (Broker et al., 2011, PMID: 21683062). Beyond vaccination, these TCR-peptide-MHC interactions are studied to understand immune memory and potential carrier-induced epitopic suppression, where pre-existing immunity to the carrier might affect the response to the conjugate (Schutze et al., 1985, PMID: 2581004).

Other names

CRM197-specific T-cell receptorDiphtheria toxoid-specific T-cell receptorCD4+ T-cell receptor for diphtheria carrier proteinsCRM197-specific TCRDT-specific TCR

The TCR recognizes and binds to specific peptides derived from CRM197 or diphtheria toxoid presented on MHC class II molecules by antigen-presenting cells, which triggers CD4+ T-cell activation, cytokine production, and provides essential help for B-cell antibody production and memory formation.