Target intelligence / Profile preview

CD4+ T-cell receptor recognizing CRM197-derived peptides (CRM197-specific TCR)

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

Overview

CD4+ T-cell receptors (TCRs) recognizing CRM197-derived peptides are essential for the immunogenicity of conjugate vaccines. CRM197 is a genetically detoxified version of the diphtheria toxin, widely used as a carrier protein to convert T-independent polysaccharide antigens into T-dependent ones (Pichichero, 2013, 'Protein carriers of conjugate vaccines'). When a conjugate vaccine is administered, antigen-presenting cells (APCs) internalize the complex and process the CRM197 protein into peptide fragments. These peptides are then loaded onto MHC class II molecules and displayed on the APC surface for recognition by specific CD4+ TCRs (Broker et al., 2011, 'CRM197 carrier protein: properties and applications'). The resulting TCR signaling triggers the activation and clonal expansion of helper T cells. These activated T cells provide critical help to B cells through CD40L-CD40 interactions and cytokine secretion, enabling class switching and high-affinity antibody production (Bottrel et al., 2004, 'Antigenicity and immunogenicity of CRM197'). This mechanism is the cornerstone of protection for vaccines against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. Monitoring the activity of these TCRs and the resulting T-cell response is a key component of evaluating vaccine efficacy and duration of immunity.

Other names
CRM197-specific T-cell receptorDiphtheria toxin CRM197-specific TCRCRM197-reactive TCRCD4+ T-cell receptors recognizing CRM197-derived peptides presented by MHC class II on antigen-presenting cells
02

Mechanism of action

Activation of CD4+ T cells via TCR recognition of MHC II-presented CRM197 peptides, leading to B-cell help and antibody production.

03

Biological functions

Immune responseT-cell activationAntigen recognitionB-cell help
04

Disease associations

InfectionBacterial infectionVaccine-preventable diseases
05

Safety considerations

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

Interacting drugs

Pneumococcal 13-valent conjugate vaccine

3 more in the full profile.

07

Biomarkers

CRM197-specific CD4+ T-cell frequencyInterferon-gamma ELISpotIL-2 secretionAnti-polysaccharide IgG titers

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