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A murine C4 molecule with reduced hemolytic efficiency

J P Atkinson, K McGinnis, L Brown

The Journal of Experimental Medicine

|February 1, 1980

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Mice with the H-2w7 haplotype show reduced complement component 4 (C4) hemolytic activity. This decreased function is linked to structural changes in the C4 alpha-chain, not inhibitors or molecule instability.

Area of Science:

Immunogenetics
Complement system biology
Molecular immunology

Background:

Complement component 4 (C4) is crucial for immune responses.
H-2 congenic mouse strains allow study of immune system variations.
The H-2w7 haplotype is associated with distinct C4 properties.

Purpose of the Study:

To investigate the functional activity of C4 in H-2-congenic mouse strains.
To determine the cause of reduced C4 hemolytic activity in strains with the H-2w7 haplotype.

Main Methods:

Assessing C4 functional activity and antigenic levels in H-2-congenic mouse strains.
Depleting nonfunctional Slp-positive molecules to measure residual Ss (C4) antigenic activity.
Comparing hemolytic efficiency across different H-2 haplotypes.

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Main Results:

Mice with the H-2w7 haplotype exhibited 25-33% of the C4 hemolytic activity per unit of Ss antigenic activity compared to other H-2 haplotypes.
This reduction in hemolytic efficiency was independent of C4 molecule lability or the presence of inhibitors.
Strains with comparable Ss (C4) and Slp antigenic concentrations showed three- to fourfold higher C4 hemolytic activity than H-2w7 strains.

Conclusions:

The reduced hemolytic efficiency of C4 in H-2w7 haplotype strains is likely due to structural alterations in the C4 alpha-chain.
These findings highlight the impact of specific H-2 haplotypes on complement system function.