Related Experiment Videos
The complement components coded in the major histocompatibility complexes and their biological activities
Insights
The complement system involves two pathways regulated by control proteins. Genetic variations in complement components C2, factor B, and C4 within the MHC influence autoimmune disease susceptibility.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- The complement system comprises two proteolytic cascade pathways with shared components and regulatory proteins.
- Key complement components (C2, factor B, C4) are encoded by genes located within the Major Histocompatibility Complex (MHC).
- These MHC-linked genes exhibit significant polymorphism, especially C4, with multiple loci and mutant forms.
Purpose of the Study:
- To elucidate the genetic organization and functional implications of complement component genes within the MHC.
- To investigate the relationship between complement gene polymorphism and susceptibility to autoimmune diseases.
Main Methods:
- Gene mapping within the MHC region of humans and mice.
- Analysis of complement component gene polymorphism, including C4.
- Assessment of haemolytic activity variations among different C4 alleles.
Main Results:
- Established the relative positions of C2, factor B, and C4 genes within the MHC.
- Identified extensive polymorphism in C4 genes, including variable locus numbers and numerous mutant alleles.
- Observed significant differences in haemolytic activity among various C4 alleles.
Conclusions:
- Complement gene organization within the MHC is conserved between humans and mice.
- C4 allele-specific differences in haemolytic activity may contribute to the observed associations between HLA haplotypes and autoimmune disease susceptibility.
- Further research into complement genetics is crucial for understanding autoimmune disease pathogenesis.
Abstract:
The complement system has two pathways of activity, both dependent on the sequential conversion of proteolytic zymogens to active proteases leading to a common lytic complex and both with control proteins which inhibit or inactivate different steps in the cascade. Three of the components--C2, factor B and C4--are coded by closely linked genes in the MHC of man and mouse and have been placed relative to each other. The genes are polymorphic, particularly C4, with variable numbers of loci as well as many mutant forms. Some alleles of C4 show strikingly different reactivities in their haemolytic activity and this may be relevant to the association of susceptibility to autoimmune diseases with particular haplotypes in this section of HLA.