OKT4 Epitope Deficiency Research Articles

Inherited OKT4 epitope deficiency in a Chinese rhesus macaque.

OKT4 is an important epitope of the CD4 molecular. Amino acid mutations in the CD4V3 region result in deficiency of the OKT4 epitope in human. Here, we firstly reported a case of hereditary deficiency of OKT4 epitope in an inbred Chinese rhesus macaque family. This epitope deficiency is due to cytosine to thymine transition and homozygote at the nucleotide position 793 of CD4 coding sequences, which leads to the replace of arginine at 265th position of CD4 molecule by tryptophan. The results reveal that OKT4 epitope deficiency is a very old phenotype and may be parentally inherited, and emphasize the importance of avoiding inbreeding in primate population breeding.

HTLV-1-associated myelopathy (HAM) with OKT4 epitope deficiency

HTLV-1-associated myelopathy (HAM) with OKT4 epitope deficiency

Human herpesvirus 7 infection of CD4+(+) T cells does not require expression of the OKT4 epitope.

To evaluate the role of the OKT4 epitope in human herpesvirus 7 (HHV-7) infection, we studied the susceptibility to HHV-7 infection of CD4+ T cells isolated from two individuals with OKT4 epitope deficiency. HHV-7-infected OKT4-Leu3a+ T cells exhibited the characteristic cytopathic effect, reactivity with HHV-7-seropositive serum by immunofluorescence and down-modulation of surface CD4 in a manner similar to HHV-7-infected OKT4+Leu3a+ T cells. A semiquantitative PCR revealed that the amounts of HHV-7 replicated in OKT4+Leu3a+ T cells and OKT4-Leu3a+ T cells were not significantly different. Although it has been reported that OKT4 monoclonal antibody efficiently inhibits HHV-7 infection, the present study demonstrated that the interaction of HHV-7 with CD4+ T cells does not require participation of the epitope defined by OKT4 monoclonal antibody.

OKT4 epitope deficiency in patients infected with the human immunodeficiency virus: a cause of underestimation of the CD4 lymphocyte count.

Two black patients who were infected with the human immunodeficiency virus (HIV) and who had hereditary deficiency of OKT4 epitope were investigated. The patients' lymphocytes lacked the OKT4 surface antigen but reacted with other monoclonal antibodies recognizing the CD4+ helper-inducer T lymphocytes. The CD4 lymphocyte count is a surrogate marker for clinical progression of HIV disease, but it could be unreliable in regard to patients with partial or complete OKT4 epitope deficiency.

Autosomal codominant inheritance and Japanese incidence of deficiency of OKT4 epitope with lack of reactivity resulting from conformational change.

A large Japanese family in which some members were homozygous or heterozygous for OKT4 epitope deficiency was studied. Homozygotes, heterozygotes, and normal individuals were identified by differences in the number 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 subjects were examined. The OKT4 epitope was not needed for internalization of CD4 molecules, and IL-2 was produced in the same amounts by these different kinds of subjects. DNA from four clones lacking OKT4 established from four individuals of this family was sequenced. As reported 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 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 incidence of homozygotes in the Japanese population was found to be 0.47% by examination of 1478 random samples, and on the basis of this value, the incidence of heterozygotes was estimated to be 12.8%.

Single amino acid substitution in the V3 domain of CD4 is responsible for OKT4 epitope deficiency

Single amino acid substitution in the V3 domain of CD4 is responsible for OKT4 epitope deficiency

Humans with OKT4-epitope deficiency have a single nucleotide base change in the CD4 gene, resulting in substitution of TRP 240 for ARG 240

The OKT4 epitope of the CD4 cell-surface protein has been shown to be polymorphic in white, black, and Japanese populations. The variable phenotypic expression is due to an alteration of the OKT4 epitope, since those persons lacking reactivity with OKT4 monoclonal antibody (mAb) are reactive with OKT4A-F mAb as well as other mAb specific for CD4. To determine the nature of this polymorphism at the gene level, we sequenced polymerase chain reaction-amplified genomic DNA containing the CD4-V3 and -V4 exons from American black subjects who are OKT4-normal, OKT4-negative heterozygous, or OKT4-negative homozygous. Comparison of the sequences revealed that the two CD4 exons are identical except for a cytosine-to-thymidine transition occurring at nucleotide position 868. This alters the first codon position of amino acid 240 and results in a tryptophan residue replacing an arginine residue. The change was also found in white and Japanese persons who are OKT4-negative.

ＯＫＴ４抗原欠損症におけるＢ型肝炎ウイルス感染についての検討

ＯＫＴ４抗原欠損症におけるＢ型肝炎ウイルス感染についての検討

193 OKT-4 Epitope deficiency as a cause of reduced “helper” T-cells in patients (Pts) at risk for human immunodeficiency virus (HIV) infection

193 OKT-4 Epitope deficiency as a cause of reduced “helper” T-cells in patients (Pts) at risk for human immunodeficiency virus (HIV) infection

A Patient with IgD (λ)-Multiple Myeloma Accompanied by OKT4 Epitope Deficiency

A Patient with IgD (λ)-Multiple Myeloma Accompanied by OKT4 Epitope Deficiency

Familial OKT4 epitope deficiency: Studies on antigen density and lymphocyte function

The family of a case of hereditary deficiency of OKT4 epitope on helper T cells was investigated. A 30-year-old woman was found to have hardly any OKT4 + T cells (0.7%, normal 24–51%), but normal OKT3, OKT8, OKT11, OKIa 1, Leu1, Leu2a, Leu3a, Leu7, and B 1 positive cells. The response to mitogens (PHA, PWM, and Con A) and helperor suppressor-T-cell functions of her peripheral lymphocytes were normal. She had normal helper-T-cell populations detected with OKT4A (39.1%) and Leu3a (39.5%) monoclonal antibodies. One of her sisters had the same defect, but other members of the family had normal lymphocyte subsets. Lymphocyte functions were also found to be normal in all family members examined. The peak position of the fluorescence intensity of OKT4 + cells was about half that of normal controls in five members of this family. Considering that these were carriers of OKT4 epitope deficiency, the OKT4 epitope abnormality was inherited as an autosomal codominant trait in this family. Similar OKT4 epitope deficiency with normal Leu3a + and OKT4A + cells was found in 38 of 8866 (0.43%) other subjects in Japan by the examination of routine blood samples.