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A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes
Published on: March 25, 2014
Heteroligomeric forms of codon 54 mannose binding lectin (MBL) in circulation demonstrate reduced in vitro function
M M Dean1, S Heatley, R M Minchinton
1Co-operative Research Centre for Vaccine Technology, at the Australian Red Cross Blood Service, Adelaide St, Brisbane, Queensland, Australia 4000. mdean@arcbs.redcross.org.au
Abstract:
Mannose binding lectin (MBL) is a pattern recognition molecule that plays a pivotal role in innate immunity. This liver derived, circulating plasma protein binds organisms displaying high-density carbohydrate structures and flags them for destruction via opsonisation and initiation of the lectin pathway of the complement cascade. The present study reveals native, oligomeric forms of human MBL in plasma from healthy blood donors of differing genotypes and correlates the relative abundance of observed molecular weight species with mannan binding activity and C4 deposition in vitro. Wild type (A/A) individuals demonstrate predominately high molecular weight MBL that correlated with high mannan binding capacity and C4 deposition. A/C individuals demonstrated predominantly low molecular weight MBL with decreased mannan binding and C4 deposition activity. A/D individuals demonstrated both high molecular weight and low molecular weight MBL with reduced mannan binding and C4 deposition predominantly seen in combination with LX promoter. We identified A/B individuals as a unique group with large variation in MBL level, mannan binding activity and C4 deposition and propose a model for C4 deposition based on differential binding of MASP.
Insights
Mannose-binding lectin (MBL) structure varies by genotype, impacting innate immunity. High molecular weight MBL in wild-type individuals correlates with stronger immune responses, while other genotypes show reduced activity.
Area of Science:
- Immunology
- Biochemistry
- Genetics
Background:
- Mannose-binding lectin (MBL) is a key pattern recognition molecule in innate immunity.
- It is a liver-derived plasma protein that initiates the lectin pathway of complement cascade.
- MBL binds to carbohydrate structures on pathogens, marking them for destruction.
Purpose of the Study:
- To investigate native, oligomeric forms of human MBL in plasma.
- To correlate MBL molecular weight species with mannan binding activity and C4 deposition across different genotypes.
- To propose a model for C4 deposition based on MBL structure and MASP binding.
Main Methods:
- Analysis of plasma from healthy blood donors with varying MBL genotypes.
- Determination of MBL oligomeric forms and molecular weights.
- In vitro assays measuring mannan binding activity and C4 deposition.
Main Results:
- Wild-type (A/A) individuals predominantly exhibit high molecular weight MBL, correlating with high mannan binding and C4 deposition.
- A/C individuals show predominantly low molecular weight MBL with reduced binding and deposition activity.
- A/D individuals display mixed molecular weights, with reduced activity often linked to the LX promoter.
- A/B individuals exhibit significant variation in MBL levels, binding activity, and C4 deposition.
Conclusions:
- MBL genotype significantly influences its oligomeric structure and functional capacity.
- The abundance of specific MBL molecular weight forms directly impacts mannan binding and complement activation (C4 deposition).
- A model is proposed for C4 deposition, highlighting the role of MASP binding to different MBL structures.
