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Combined Immunodeficiency Caused by a Transactive Regulatory Mutation: A New Mutational Class

  • Donald A. Pious

Abstract

Our laboratory research has focused on the genes, gene regulation, protein structure, and function of HLA, the human major histocompatibility complex (MHC) of humans. In this paper I will focus on our work on HLA gene regulation and its defects as newly recognized causes of combined immunodeficiency. The HLA complex is a cluster of genes located on the short arm of chromosome six. HLA class II genes code for the heterodimeric cell surface glycoproteins HLA-DR, -DQ and -DP; both the heavy (A) and light (B) chain genes of class II molecules are in the MHC cluster. HLA class II molecules are expressed on B cells, activated T cells, macrophages, and some epithelial and other cells. In some cells, the levels of class II expression are coordinately increased by γ-interferon, IL-4, or tumor necrosis factor (TNF). Class II molecules function by binding peptides derived from degraded exogenous protein antigens; the generation by cells of immunogenic peptides from soluble exogenous proteins is known as antigen processing. The resulting peptide class II complex “presents antigen to” (ie, activates) specific helper or suppressor T cells by binding to a peptide-and HLA class II antigen-specific T cell receptor, expressed clonally. The ability of HLA molecules to bind given peptides is allele specific; the high degree of polymorphism in these genes therefore results in genetic differences in the capacity to mount immune responses to particular immunogens. In addition, certain HLA alleles are strong susceptibility factors for particular auto-immune diseases.

Keywords

Major Histocompatibility Complex Somatic Cell Hybrid Severe Combine Immunodeficiency Human Major Histocompatibility Complex Transcriptional Regulatory Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • Donald A. Pious
    • 1
  1. 1.Department of Pediatrics, Immunology and GeneticsUniversity of WashingtonSeattleUSA

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