Expression of the OKT monoclonal antibody defined antigenic determinants in malignancy

Melvyn Greaves, Domenico Delia, Robert Sutherland, Jagdish Rao, Winston Verbi, John Kemshead, Gita Hariri, Gideon Goldstein, Patrick Kung

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Monoclonal antibodies OKT1,3,4,6,8,9,10,11 and 11A have been screened by immunofluorescence (FACS and microscopy) and 125I-binding assays for their cellular specificity in human leukaemia in relation to other cell markers (e.g. cALL gp100 antigen, HLA-DR, TdT, E rosettes). In a series of 69 T cell malignancies a distinctive correlation was observed between phenotype and clinical diagnosis. In every instance, T-ALL cells have an immature or early thymic phenotype and T non-Hodgkin lymphoma have a predominant cortical thymic phenotype indicating that these two malignancies originate from T cell precursors. In contrast, adult T-Sezary leukaemia, T-CLL and T-PLL have mature T cell subset phenotypes, the majority being T3+ T4+ T8- /TdT- "helper/inducer" cell types and are presumed to originate in mature immunocompetent T cells. OKT11 and OKT11A give concordant reactions with E (sheep) rosettes and appear to react with the same receptor structure. The composite phenotype of several T-ALL cell lines can be modulated in vitro by phorbol ester (TPA). HPB-ALL, for example, loses TdT and OKT4 binding, decreases OKT9, maintains OKT8 and increases OKT1, HLA-ABC and OKT11 binding and E rosettes. OKT9 reacts preferentially in T leukaemias with T-ALL but is not T specific. It binds to many types of leukaemias and to malignant cell lines e.g. teratocarcinoma, melanoma, colon carcinoma and neuroblastoma. Normal foetal thymus, foetal liver and lectin activated T cells are also positive. Cell separation experiments indicate that OKT9 determinant is clearly associated with cell proliferation status although not cycle phase specific. When leukaemic cells (such as HL-60, HPB-ALL) are induced to mature in vitro by retinoic acid or TPA, respectively, the OKT9 determinant is lost. Biochemical studies indicate that OKT9 reacts with a gp 90K dalton dimer which appears to be the receptor for transferrin. This monoclonal antibody defined structure is probably the same as that described by Onary with monoclonal B3/25 and by Bramwell and Harris. The latter believed the structure to be a specific marker of malignancy. Some other OKT monoclonals are not T lineage specific. OKT10 binds to leukaemias and normal marrow cells of the myeloid and B cell lineages. OKT6 binds to neuroblastoma cells as does a similar monoclonal, NA134/HTA-1.

Original languageEnglish
Pages (from-to)283-299
Number of pages17
JournalInternational Journal of Immunopharmacology
Issue number3
Publication statusPublished - 1981

ASJC Scopus subject areas

  • Immunology
  • Pharmacology


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