MHC Class II‐Deficient Combined Immunodeficiency: A Disease of Gene Regulation

MHC class Il-deficient combined immunodeficiency, or MHC class II deficiency, also referred to as the Bare Lymphocyte Syndrome (BLS), is a rare severe primary immunodeficiency characterized by a lack of HLA class II gene expression. In contrast to the majority of hereditary diseases, in particular other primary immunodeficiencies, the genetic defect responsible for MHC class II deficiency does not reside in the genes directly responsible for the phenotype of the patients, namely the HLA class II genes themselvesInstead, the defect lies in trans-acting factors controlling expression of HLA class II genes. MHC class II immunodeficiency thus represents a disease of gene regulation (de Preval et al. 1985), an unusual situation in human medical genetics. Tight regulation of MHC class II gene transcription controls quantitative variations in cell surface expression of MHC class II antigens, and thus plays a key role in the control of the immune response (Janeway et al. 1984). The molecular mechanisms underlying MHC class II gene expression have consequently been studied intetisively. In this context, MHC class II deficiency has provided a unique genetic model system that has facilitated the recent characterization and cloning of trans-acting factors required for expression of MHC class II genes.

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