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T-cell receptor on CD4+ T helper cells recognizing CRM197 peptide–MHC II complexes

Molecular classification
Receptor, T-cell receptor complex, Immunoglobulin superfamily
01

Overview

The T-cell receptor (TCR) on CD4+ T helper cells recognizing CRM197 peptide–MHC II complexes is a pivotal immunological target in the context of conjugate vaccine technology (PubMed: 21939738). CRM197 is a genetically detoxified mutant of the diphtheria toxin (G52E) that contains multiple universal T-cell epitopes capable of binding a wide array of human MHC Class II alleles (UniProt: P00588). Upon vaccination, antigen-presenting cells internalize the conjugate, process the CRM197 carrier, and present its peptides via MHC II to specific CD4+ T cells. The resulting TCR-mediated activation of these T helper cells is essential for inducing B-cell isotype switching and memory formation against the conjugated polysaccharide antigens, which are otherwise poorly immunogenic (PubMed: 24003153). This mechanism is the foundation for several widely used vaccines targeting pathogens such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b (StatPearls: NBK537114). Understanding the interaction between this TCR and the CRM197-MHC II complex is crucial for optimizing vaccine design and ensuring robust, long-lasting protective immunity across diverse populations.

Other names
CRM197-specific T-cell receptorTCR recognizing diphtheria toxin mutant CRM197CD4+ TCR for CRM197T-cell receptor for Cross-Reacting Material 197
02

Mechanism of action

The T-cell receptor recognizes CRM197-derived peptides presented by MHC Class II molecules on antigen-presenting cells, which triggers CD4+ T-cell activation and the provision of cognate help to B cells for high-affinity antibody production (PubMed: 21939738).

03

Biological functions

Immune responseT-cell activationAntigen recognitionB-cell helpCytokine production
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Disease associations

Infection
05

Safety considerations

Hypersensitivity to CRM197 or diphtheria toxoidInjection site inflammationCarrier-induced epitopic suppression (PubMed: 10417048)
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Interacting drugs

Pneumococcal 13-valent Conjugate Vaccine (Prevnar 13)

4 more in the full profile.

07

Biomarkers

CRM197-specific CD4+ T-cell frequencyAnti-polysaccharide IgG antibody titersInterferon-gamma (IFN-g) productionInterleukin-4 (IL-4) production (PubMed: 24003153)

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