T-cell receptor specific for CRM197-derived peptide–MHC II complexes (TCR-CRM197-MHCII)

T-cell receptors (TCRs) specific for CRM197-derived peptide–MHC II complexes are specialized immune receptors found on the surface of CD4+ T lymphocytes that recognize processed fragments of the CRM197 protein. CRM197 is a genetically detoxified mutant of the diphtheria toxin (G52E) that serves as a highly effective carrier protein in conjugate vaccines, such as those against Streptococcus pneumoniae and Neisseria meningitidis (Bröker et al., 2011). These TCRs play a critical role in the carrier effect, where the recognition of CRM197 peptides presented by Major Histocompatibility Complex (MHC) Class II molecules on B cells or dendritic cells triggers T-cell activation and the subsequent provision of help for B-cell antibody production (Pecetta et al., 2016). This interaction is essential for converting T-cell independent polysaccharide antigens into T-cell dependent antigens, thereby inducing long-term immunological memory and high-affinity IgG responses (Avci et al., 2011). In clinical practice, these TCRs are the primary targets of conjugate vaccines, and their activation is monitored to assess vaccine immunogenicity and the breadth of the immune response (Rappuoli, 2018). Understanding the specific TCR repertoires and MHC II restrictions associated with CRM197 is vital for optimizing vaccine design and potentially developing novel immunotherapies that utilize CRM197 as a scaffold for delivering antigens (Bottazzi et al., 2015).

Other names

CRM197-specific T-cell receptorDiphtheria toxin mutant-specific TCRAnti-CRM197 TCRCRM197-reactive T-cell receptor

Binding of the T-cell receptor to the CRM197 peptide-MHC II complex initiates a signaling cascade that leads to CD4+ T-cell activation, cytokine secretion, and subsequent B-cell help for antibody production.