AUTOSOMAL CODOMINANT INHERITANCE AND JAPANESE INCIDENCE OF DEFICIENCYOF OKT4 EPITOPE WITH LACK OF REACTIVITY RESULTING FROM CONFORMATIONALCHANGE

A large Japanese family in which some members were homozygous or heter ozygous for OKT4 epitope deficiency was studied. Homozygotes, heterozy gotes, and normal individuals were identified by differences in the nu mber of OKT4 epitopes on the surfaces of lymphocytes. This deficiency was transmitted as an autosomal codominant trait. The internalization of CD4 molecules and the production of IL-2 by lymphocytes of these su bjects were examined. The OKT4 epitope was not needed for internalizat ion of CD4 molecules, and IL-2 was produced in the same amounts by the se different kinds of subjects. DNA from four clones lacking OKT4 esta blished from four individuals of this family was sequenced. As reporte d elsewhere for different subjects, a single nucleotide substitution ( CGG --> TGG) was found in all four cell lines. The mutation results in arginine being replaced by tryptophan. Analysis showed different hydr ophobicity at positions 239 and 240 from the control, probably giving rise to a conformational change in CD4 accounting for lack of reactivi ty with the OKT4 monoclonal antibody. The incidence of homozygotes in the Japanese population was found to be 0.47% by examination of 1478 r andom samples, and on the basis of this value, the incidence of hetero zygotes was estimated to be 12.8%.