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

The T-cell receptor (TCR) recognizing CRM197-derived peptide–MHC-II complexes is a fundamental mediator of the immune response to conjugate vaccines. CRM197, a non-toxic mutant of the diphtheria toxin (G52E), is widely utilized as a carrier protein to enhance the immunogenicity of polysaccharide antigens (Pecetta et al., 2016, PMID: 27149147). Upon vaccination, CRM197 is internalized by antigen-presenting cells, proteolytically processed, and its peptides are presented on the cell surface by Major Histocompatibility Complex class II (MHC-II) molecules, particularly HLA-DR (Gianni et al., 2018, PMID: 30108576). CD4+ helper T cells possessing TCRs specific for these CRM197 peptide-MHC complexes are then activated. These activated T cells provide the necessary signals, such as CD40L and cytokines, to B cells, enabling them to undergo class-switch recombination and affinity maturation against the conjugated polysaccharide (Bottegoni et al., 2011, PMID: 21148035). This mechanism transforms a T-cell-independent response into a T-cell-dependent one, ensuring long-lasting immunity and memory. Understanding the repertoire and specificity of these TCRs is vital for optimizing vaccine design and ensuring broad population coverage across different HLA alleles (FDA, Prevnar 13 Package Insert).

Other names

CRM197-specific T-cell receptorCD4+ T-cell receptor for CRM197T-cell receptor for Cross-Reacting Material 197Helper T-cell receptor for diphtheria toxin mutant CRM197

Activation of CD4+ helper T cells through the recognition of CRM197 peptides presented by MHC-II, which facilitates B-cell activation, isotype switching, and high-affinity antibody production against conjugated antigens.