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The polymorphism of the complement genes in HLA.

R R Porter

    Annales De L'Institut Pasteur. Immunologie
    |January 1, 1985
    PubMed
    Summary

    The human leukocyte antigen (HLA) complex contains genes for complement proteins C2, C4A, C4B, and factor B. Despite significant genetic variation in complement component 4 (C4) forms, their amino acid sequences are remarkably similar.

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    Area of Science:

    • Immunogenetics
    • Molecular Biology
    • Human Leukocyte Antigen (HLA) Complex

    Background:

    • The human leukocyte antigen (HLA) complex, a region of critical importance in the immune system, harbors genes encoding complement proteins C2, C4A, C4B, and factor B.
    • Complement proteins, particularly C4, exhibit extensive polymorphism, including variations in gene copy number and allelic diversity, contributing to genetic complexity within the HLA region.

    Purpose of the Study:

    • To investigate the genetic complexity and allelic variations of complement proteins C2, C4A, C4B, and factor B within the human leukocyte antigen (HLA) complex.
    • To explore the functional implications of C4 polymorphism, including differences in reactivity and hemolytic activity.
    • To examine the relationship between HLA haplotypes, C4 genetic variations, and susceptibility to autoimmune diseases.

    Main Methods:

    • Analysis of gene loci for complement proteins C2, C4A, C4B, and factor B within the HLA complex.
    • Characterization of C4 polymorphism, including gene deletions, duplications, and allelic variations.
    • Assessment of the reactivity of different C4 forms with small molecules and their hemolytic activity.
    • Comparison of amino acid sequences between allelic forms of C4A and C4B.

    Main Results:

    • Significant polymorphism was observed for complement components, especially C4, with numerous alleles and variations in gene loci copy number.
    • Different C4 variants displayed distinct reactivities with small molecules and varying hemolytic activities within the complement system.
    • Despite functional differences, amino acid sequences of allelic C4 forms showed high similarity, with less than 1% residue variation between C4A and C4B alleles.

    Conclusions:

    • The genetic architecture of C4 within the HLA complex is complex, involving multiple loci, copy number variations, and extensive allelic diversity.
    • The observed functional differences in C4 variants, despite sequence similarity, suggest subtle yet significant molecular mechanisms influencing complement system activity.
    • These findings may provide insights into the association between specific HLA haplotypes and increased susceptibility to autoimmune diseases.

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