Target intelligence / Profile preview

CRM197-derived peptide-MHC class II complex (CRM197-pMHCII)

Target
CRM197-pMHCII
Molecular classification
Antigen-MHC complex, Protein complex
01

Overview

CRM197-derived peptide epitopes bound to MHC class II represent the functional immunological unit responsible for the carrier effect in conjugate vaccines (Source: PubMed PMID 24055317). CRM197 is a non-toxic mutant of the diphtheria toxin, specifically featuring a glycine-to-glutamic acid substitution at position 52 (G52E), which eliminates its ADP-ribosyltransferase activity (Source: UniProt P00588). In the context of vaccination, antigen-presenting cells (APCs) such as dendritic cells internalize CRM197-polysaccharide conjugates and proteolytically process the CRM197 protein into various peptide epitopes (Source: PubMed PMID 11544333). These peptides are subsequently loaded onto Major Histocompatibility Complex (MHC) class II molecules for presentation on the cell surface. This peptide-MHC II complex is the primary target for T-cell receptors (TCRs) on CD4+ T-helper cells. Recognition of these specific CRM197 epitopes triggers T-cell activation and the secretion of cytokines, which are essential for driving B-cell differentiation into plasma cells and memory cells, thereby ensuring a high-affinity IgG response against the linked polysaccharide (Source: PubMed PMID 21148615). The use of CRM197 as a carrier is a cornerstone of modern vaccinology, enabling protection against encapsulated bacteria in infants and the elderly.

Other names
CRM197 epitopesCross-reacting material 197 peptide-MHC II complexDiphtheria toxin CRM197 mutant epitopesCRM197-MHCII
02

Mechanism of action

The complex acts as a ligand for T-cell receptors (TCRs) on CD4+ T-helper cells, triggering T-cell activation and subsequent B-cell help for high-affinity antibody production against conjugated polysaccharides.

03

Biological functions

Antigen presentationT-cell activationImmune response inductionB-cell help
04

Disease associations

InfectionBacterial infection (prevention)
05

Safety considerations

Carrier-induced epitopic suppression (CIES)Hypersensitivity reactionsPre-existing immunity interference
06

Interacting drugs

Pneumococcal 13-valent conjugate vaccine (Prevnar 13)

4 more in the full profile.

07

Biomarkers

CRM197-specific CD4+ T-cell proliferationCytokine release (e.g., IL-2, IFN-gamma, IL-4)CRM197-specific T-cell frequency (ELISpot)Anti-CRM197 IgG antibody titers

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