Target intelligence / Profile preview

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

Target
CRM197-specific TCR
Molecular classification
Receptor, T cell receptor, Protein complex
01

Overview

The CD4+ T cell receptor (TCR) recognizing CRM197 peptide–MHC class II complexes is a specialized immune receptor essential for the efficacy of conjugate vaccines. CRM197 is a non-toxic mutant of the diphtheria toxin (Gly52Glu) that acts as a carrier protein to convert T-cell independent polysaccharide antigens into T-cell dependent ones (Pecetta et al., 2016). When a conjugate vaccine is administered, antigen-presenting cells (APCs) internalize the complex and process CRM197 into peptides, which are then presented on Major Histocompatibility Complex (MHC) class II molecules (Broker et al., 2011). Specific TCRs on the surface of CD4+ T cells bind to these peptide-MHC II complexes, initiating a signaling cascade that leads to T-cell activation and the secretion of cytokines like IL-4 and IL-21. This T-cell activation is crucial for providing help to B cells, enabling them to undergo isotype switching and affinity maturation to produce high-titer, long-lasting antibodies against the target pathogen (Bottrel et al., 2004). Consequently, these TCRs are primary targets for monitoring vaccine immunogenicity and are central to the design of next-generation glycoconjugate vaccines.

Other names
CRM197-specific T-cell receptorTCR recognizing CRM197-MHCIIDiphtheria toxoid-specific T-cell receptorCRM197-specific CD4+ T cell receptor
02

Mechanism of action

CRM197-derived peptides are presented by MHC class II molecules to specific TCRs on CD4+ T cells, triggering T-cell activation and subsequent B-cell help for antibody production.

03

Biological functions

Immune responseAntigen recognitionT cell activationB cell help
04

Disease associations

InfectionProphylaxis
05

Safety considerations

Carrier-induced epitopic suppressionHypersensitivity to diphtheria toxoidPre-existing immunity interference
06

Interacting drugs

Pneumococcal 13-valent conjugate vaccine

3 more in the full profile.

07

Biomarkers

CRM197-specific CD4+ T cell frequencyIFN-gamma productionIL-2 productionMHC II tetramer bindingAnti-CRM197 antibody titers

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