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HLA-linked immune suppression genes.

T Sasazuki1

  • 1Department of Genetics, Kyushu University, Fukuoka, Japan.

Jinrui Idengaku Zasshi. the Japanese Journal of Human Genetics
|March 1, 1990
PubMed
Summary
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Human immune responses are genetically controlled, with specific genes influencing low responsiveness to antigens. These immune suppression genes, linked to HLA-DQ, involve CD8+ T cells and are epistatic to HLA-DR, regulating immune responses.

Area of Science:

  • Immunogenetics
  • Human immune response regulation
  • HLA system

Background:

  • Human immune responses to natural antigens exhibit significant individual variability, categorized as high or low responders.
  • Previous studies suggested genetic factors influence immune response levels, but the specific mechanisms remained unclear.

Purpose of the Study:

  • To investigate the genetic control of immune response variations in humans.
  • To identify specific genes and genetic loci associated with low immune responsiveness.
  • To elucidate the roles of HLA-DR and HLA-DQ in immune response regulation.

Main Methods:

  • Family and population-based genetic analyses of immune responses to various natural antigens.
  • Investigation of CD8+ T cell function in low responders.

Related Experiment Videos

  • In vitro studies using monoclonal antibodies against HLA-DR and HLA-DQ.
  • Analysis of antigen-specific T cell lines from low responders.

    • Main Results:

    • Low responsiveness to streptococcal cell wall antigen (SCW) is an HLA-linked dominant trait.
    • CD8+ suppressor T cells are present in low responders and their depletion restores immune response.
    • Immune suppression genes for SCW are in linkage disequilibrium with HLA-DQ alleles.
    • Similar associations were observed for other antigens (schistosomal, Mycobacterium leprae, tetanus toxoid, pollen, hepatitis B).
    • Anti-HLA-DQ antibodies restored immune response in low responders, while anti-HLA-DR inhibited high responders.
    • HLA-DQ is epistatic to HLA-DR in immune regulation.
    • HLA-DQ-restricted CD4+ T cells activate CD8+ suppressor T cells, downregulating immune response.

    Conclusions:

    • HLA-linked immune suppression genes exist in humans, controlling low responsiveness to natural antigens.
    • HLA-DQ plays a dominant role in downregulating immune responses, potentially through CD8+ T cell activation.
    • HLA-DR appears to upregulate immune responses, with HLA-DQ exhibiting epistasis over HLA-DR.