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Major histocompatibility complex class II (MHC II) on antigen-presenting cells presenting CRM197-derived glycopeptides (MHC II)

Target
MHC II
Molecular classification
Major histocompatibility complex, Receptor, Glycoprotein complex
01

Overview

Major histocompatibility complex class II (MHC II) molecules are transmembrane glycoproteins expressed on professional antigen-presenting cells (APCs) such as dendritic cells, B cells, and macrophages (StatPearls, 2023). Their primary biological function is to present processed exogenous peptides to the T-cell receptors (TCRs) of CD4+ helper T cells, thereby initiating and modulating the adaptive immune response. In the context of conjugate vaccines, CRM197 (a non-toxic mutant of diphtheria toxin) serves as a carrier protein that is internalized and proteolytically processed by APCs into various fragments, including glycopeptides where the vaccine's polysaccharide antigen remains covalently attached to a CRM197-derived peptide (Avci et al., 2011). The presentation of these CRM197-derived glycopeptides by MHC II is a critical step in converting a T-cell independent carbohydrate response into a T-cell dependent one, facilitating B-cell isotype switching, affinity maturation, and the development of long-term immunological memory (Pichichero, 2013). This mechanism is the foundation for several highly successful vaccines targeting bacterial pathogens like Streptococcus pneumoniae and Neisseria meningitidis (Bröker et al., 2011). By specifically targeting the MHC II pathway with these glycopeptides, vaccines can induce robust protection in populations with immature or compromised immune systems, such as infants.

Other names
HLA class IIMHC-IIMajor histocompatibility complex type IIHuman leukocyte antigen class IIMHC II-CRM197 complexpMHCII complex
02

Mechanism of action

Carrier protein processing and presentation of glycopeptides to CD4+ T cells to induce T-cell dependent antibody responses.

03

Biological functions

Antigen presentationImmune responseT-cell activationB-cell maturationImmunological memory formation
04

Disease associations

InfectionPneumococcal diseaseMeningococcal diseaseHaemophilus influenzae type b infection
05

Safety considerations

Hypersensitivity to diphtheria toxoidInjection site reactions (erythema, swelling)Systemic inflammatory response (fever, malaise)Carrier-induced epitopic suppression
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Interacting drugs

13-valent pneumococcal conjugate vaccine (Prevnar 13)

4 more in the full profile.

07

Biomarkers

CRM197-specific CD4+ T-cell activationAnti-polysaccharide IgG antibody titersMemory B-cell frequency (CD27+)Cytokine production (IL-4, IFN-gamma)

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