We have recently derived a series of cloned cell lines displaying natural killer (NK) cell-like activity from normal human fetal blood (25 weeks). The lines were obtained after repeated stimulation of mononuclear cells with allogeneic Epstein-Barr virus (EBV)-transformed B lymphocytes and are interleukin-2 (IL-2) dependent. Initial characterization of the clones has been reported previously. Certain of these clones have been found to have unusual surface characteristics, namely, they are recognized by several well-defined anti-T3 antibodies, but do not react with WT31, which is thought to recognise an invariant epitope of the human (Ti-alpha beta) structure. Transcription of the genes encoding the alpha- and beta-chains of the T-cell receptor was assessed in two of these clones (F6A4 and F6C7). Ti-beta genes were found to be expressed, whereas alpha messenger RNA was not detected in Northern blot analysis. These data strongly suggest that these cells do not produce a stoichiometric T3/Ti-alpha beta receptor complex. However, experiments performed with a monoclonal antibody (anti-NKFi) developed against F6C7 cells demonstrated the existence of a unique clonotypic structure [relative molecular mass (Mr) 85,000 (85K)] which is surface-associated with T3 proteins. Furthermore, both anti-T3 and anti-NKFi were found to block cytotoxic effector function. Together, the results support the view that T3 proteins are involved in non-major histocompatibility complex (MHC)-restricted cytotoxic reactions mediated by certain circulating fetal lymphocytes which are likely to use a clonotypic structure distinct from both the 'first' (alpha beta) and the putative 'second' (gamma delta) T-cell receptor to recognize their target. The present studies were designed to characterize this structure.

Antibodies, Monoclonal↗

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A gamma-chain complex forms a functional receptor on cloned human lymphocytes with natural killer-like activity.

We have recently derived from human fetal blood (25 wks) a series of cloned cell lines that were selected for their ability to kill the conventional natural killer (NK) target cell K562. It was found that a fraction of these clones express CD3 proteins but not the monomorphic Ti alpha beta determinant recognized by WT31 antibody. One interleukin-2-dependent CD3+ WT31- clone, termed F6C7, was used for immunization of mice to generate monoclonal antibodies directed at a potentially novel recognition receptor. It was shown that F6C7 cells, which transcribe Ti beta but not Ti alpha genes, surface-express a clonotypic structure, termed NKFi. Immunoprecipitations performed with anti-NKFi monoclonal antibody (mAb) indicated that the corresponding molecule is resolved in SDS-polyacrylamide gel electrophoresis (PAGE) as a single band of relative molecular mass approximately 85,000 (Mr approximately 85K). After reduction, a major band was detected at 44K and a faint band was present at 41K. The present study was designed to characterize this structure. It was found that NKFi represents either two 44K disulphide-linked gamma (TCR) chains, or possibly one gamma chain associated to an additional undetected molecule, and that the 41K material corresponds to a partially glycosylated fraction of the gamma protein. Anti-NKFi mAb both induces a specific autocrine proliferative response and blocks cytotoxic function, demonstrating that gamma chains serve as functional receptor structures on subpopulations of normal human lymphocytes.

Antibodies, Monoclonal↗

PubMedDate not supplied

[An update on tools].

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Biology↗

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[Importance of monoclonal antibodies in the analysis of tumor markers].

Due to their extreme specificity, monoclonal antibodies (Mabs) have been very useful for new analytical progresses in the field of tumor markers. For example, it has been possible to analyse only calcitonin, independently of its precursors in the patients with medullary thyroid carcinomas. These precursors have been estimated and found increased in the absence of calcitonin for many cancer patients, specially with small cell lung tumors. The assay of HCG and its subunits with a great specificity and sensitivity is an other interesting example of the analytical power of Mabs. The usefulness of the assay of beta subunit is now clear in the diagnostic and follow up of choriocarcinoma and perhaps in the screening of high risk pregnancies. An other example can be derivated of our works on neuropeptide Y (NPY). The assay of NPY is highly difficult, due to its great similarity with other neuropeptides (PYY and PP). Mabs have been used to solve these analytical problems. The assay of NPY is useful not only for patients with neuroendocrine tumors, but also experimentally in the rat hypothalamus for research in nutrition.

Amino Acid Sequence↗

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In vitro evaluation of drug-induced toxic effects on the immune system as assessed by proliferative assays and cytokine production.

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Amoxicillin↗

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[Effect of chronic chloroquine poisoning on the cardiac binding sites of calcium inhibitors in the rat].

Among the antimalarial drugs, chloroquine (CLQ) and 4-aminoquinoline derivatives display important interferences with biological membranes. The present study reports the effects of CLQ on dihydropyridine binding sites, measured in the heart of rats intoxicated with the drug. Acute intoxication does not entail any modification of the sites. On the other hand, binding sites were dramatically decreased by a chronic intoxication realized twice a week. In such a case, this decrease may be directly related to CLQ concentration in the heart. The regulation mechanisms involved are discussed.

Animals↗

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