Combined immunodeficiency with defective expression in major histocompatibility complex class II genes.

There are many examples of inherited immunodeficiencies characterized by normal differentiation of T and B lymphocytes but abnormal functions of these cells. Among them, combined immunodeficiency with defective expression in MHC class II genes was the first to be individualized. It is called MHC class deficient SCID by the WHO committee for the classification of immunodeficiency. It is an autosomal recessive disease with a severe evolution. Most of the 30 patients described died unless they were transplanted with HLA identical or HLA mismatched bone marrow. All HLA class II molecules (DR, DQ, and DP specificities) are absent on the cell surface in all tissues while HLA class I molecules are detectable. T and B cell abnormalities are characterized by defective in vivo and in vitro responses to antigens, although in vitro reactivity to mitogens is normal. These anomalies are considered as a direct consequence of the absence of HLA class II molecules on the surface of antigen-presenting cells incapable of sensitizing T cells. It was strongly suggested that MHC class II deficient SCID is due to a mutation that affects the regulation of the expression of all genes involved in the synthesis of MHC class II molecules.