[Abnormality of CD4 molecule--OKT4 epitope deficiency].

The individuals with OKT4 epitope deficiency are identified as incomplete (heterozygote carriers) and complete (homozygotes) by the difference in the number of OKT4 epitopes on the surface of lymphocytes. The incidence of homozygotes in the Japanese population was found to be 0.47% by examination of 1,478 random samples, and on the basis of this value, the incidence of heterozygotes was estimated to be 12.8% by the Hardy-Weinberg's formula. This deficiency was transmitted as an autosomal codominant trait. DNA from the lymphocytes with complete OKT4 epitope deficiency from the members of three families was sequenced, and a single nucleotide base substitution (CGG-->TGG) was found. This mutation was confirmed to be responsible for OKT4 epitope deficiency by using the mouse L cells transfected with mutant CD4 cDNA. The mutation results in arginine being replaced by tryptophan. Analysis showed different hydrophobicity at positions 239 and 240 from the control, probably giving rise to a conformational change in CD4 accounting for lack of reactivity with the OKT4 monoclonal antibody. The lymphocytes with OKT4 epitope deficiency did not show any abnormality in their susceptibility to HIV infection, the internalization of CD4 molecules by TPA-treatment, the capability of producing IL-2 in vitro, and the expression of IL-2 receptors (alpha/beta-chain) by PHA-stimulation.