CD4+ T-cell receptor recognizing CRM197-MHC class II peptide complex (TCR-CRM197-MHCII)

The CD4+ T-cell receptor (TCR) recognizing the CRM197-MHC class II peptide complex is a pivotal immunological target in the context of conjugate vaccine technology (Pichichero, 2013; PMID: 23414947). CRM197 is a genetically detoxified version of the diphtheria toxin, specifically the Gly52Glu mutant, that acts as a highly immunogenic carrier protein for polysaccharide antigens (Broker et al., 2011; PMID: 21621648). In the immune system, this TCR specifically binds to peptides derived from CRM197 when they are presented on the surface of antigen-presenting cells (APCs) or B cells via Major Histocompatibility Complex (MHC) class II molecules (Avci et al., 2011; PMID: 21796118). This recognition event triggers the activation of CD4+ T-helper cells, which subsequently provide the necessary signals, such as CD40 ligand expression and cytokine secretion, to B cells. This T-cell help is essential for converting T-cell independent polysaccharide antigens into T-cell dependent ones, enabling B-cell class switching and the formation of long-lived memory B cells (Shiny et al., 2021; PMID: 33859104). Drugs or biologicals interacting with this target include various conjugate vaccines targeting Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. By engaging this TCR, these vaccines ensure robust and durable protective immunity against life-threatening bacterial infections.

Other names

CRM197-specific T-cell receptorDiphtheria toxin CRM197-specific TCRTCR-CRM197-MHCII complexCD4+ TCR for CRM197

Activation of CD4+ T-helper cells through TCR-mediated recognition of CRM197 peptides presented on MHC class II molecules, which induces cytokine production and provides essential help for B-cell maturation and antibody production.