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T-cell receptor recognizing CRM197-derived peptides presented on MHC class II (TCR-CRM197-MHCII)

Target
TCR-CRM197-MHCII
Molecular classification
Receptor, T-cell receptor, Antigen-specific receptor, Immune system protein
01

Overview

The T-cell receptor (TCR) recognizing CRM197-derived peptides presented on MHC class II is a specialized immune receptor that plays a pivotal role in the efficacy of conjugate vaccines (Pecetta et al., 2016). CRM197, a non-toxic mutant of the diphtheria toxin, is widely utilized as a carrier protein because it contains potent T-cell epitopes that stimulate robust CD4+ T-cell responses (Bröker et al., 2011). These TCRs specifically bind to CRM197 fragments processed and presented by Major Histocompatibility Complex (MHC) class II molecules on antigen-presenting cells. This interaction triggers T-cell activation and the subsequent provision of "help" to B-cells, which is essential for generating high-affinity antibodies and long-term immunological memory against the vaccine's primary antigen (Rappuoli, 2018). Research into these specific TCRs helps in understanding individual variations in vaccine responsiveness and aids in the design of next-generation immunotherapies. The specificity of these receptors is determined by their unique complementarity-determining regions (CDRs) which interact with the peptide-MHC complex (Baxendale et al., 2000). These TCRs are not only targets for vaccine-induced activation but are also being explored in the context of engineered T-cell therapies to enhance immune responses against various pathogens and potentially tumors.

Other names
CRM197-specific T-cell receptorTCR specific for diphtheria toxin mutant CRM197CRM197-restricted T-cell receptorT-cell receptor alpha/beta (CRM197-specific)
02

Mechanism of action

The T-cell receptor (TCR) specifically binds to CRM197-derived peptides presented by MHC class II molecules on the surface of antigen-presenting cells. This binding event triggers a signaling cascade within the T-cell, leading to activation, proliferation, and the secretion of cytokines that support B-cell maturation and antibody production against the conjugated antigen.

03

Biological functions

Immune responseAntigen recognitionT-cell activationAdaptive immunityCytokine productionHelper T-cell function
04

Disease associations

InfectionInfectious disease prophylaxisBacterial infection
05

Safety considerations

Cytokine release syndrome (CRS)Off-target reactivity with self-peptidesImmune-mediated adverse eventsAnaphylaxis to carrier proteinMolecular mimicry
06

Interacting drugs

CRM197

4 more in the full profile.

07

Biomarkers

HLA-DRB1 allelesInterferon-gamma (IFN-g) productionTCR beta chain CDR3 sequenceCD4+ T-cell countCRM197-specific T-cell frequency

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