Genes Encoding the T-Cell Antigen Receptor

Mak, Tak W.; Caccia, Nicolette; Cook, T.; Vadasz, Veronica; Yoshikai, Yasunobu; Sohn, Uik; Kimura, N.; Toyonaga, Barry

doi:10.1111/1523-1747.ep12275570

Cited by 4 publications

(1 citation statement)

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“…The events conse quent to antigen recognition -namely, cellular prolifera tion, development of killer cells, and regulatory func tions, are thus initiated. In contrast to the immunoglobu lin genes, the antigen recognition structure creates its specificities in the same pattern and has its own set of genes [20].…”

Section: Blocking Effect Of Okt3 On Established Killer Cellsmentioning

confidence: 99%

Monoclonal Antibody Specificity: Orthoclone OKT3 T-Cell Blocker

Goldstein¹

1987

Nephron

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Orthoclone OKT3, a murine monoclonal antibody of the IgG2a class, was initially developed as a pan-T cell monoclonal antibody for use as a marker to differentiate between cell subsets. Only later did its potential role in treating allograft rejection become apparent. At first, its mechanism of action in such cases was not understood. Subsequent investigations demonstrated that OKT3 not only removed all T cells, but also specifically interacted with the T3 antigen recognition complex found on late thymocytes and mature T cells, consequently blocking the immunologic function of these cells. When injected into a patient, OKT3 can act in three ways to reverse allograft rejection. It initially coats, or opsonizes, the circulating T cells, which are then removed by the reticuloendothelial cells in the liver and spleen. OKT3 also modulates the T3 antigen recognition complex of circulating T cells, producing cells with all their phenotypic characteristics, except for the T3 molecules and the antigen recognition complex. The key mechanism of action of OKT3 in treating allograft rejection may be its ability to block the killer function of sessile T cells. In contrast to polyclonal antiserums, each molecule of OKT3 monoclonal antibody is virtually identical and has an identical specificity, thereby producing consistent reactivity to human T cells with a defined and relatively low degree of toxicity. Although derived from a hybridoma and grown in mouse ascites, OKT3 undergoes numerous purification steps to ensure that the final product is sterile, biochemically pure, homogeneous IgG2a. Furthermore, each batch is checked to make sure that its functional activity is the same as the standard. The potential usefulness of OKT3 has not been diminished by the fact that, as a murine protein, it can elicit a host-antibody response. This is because therapy (5 mg/day, i.v.) is successful in most cases within 10–14 days. Therefore, therapy can be completed before antibodies have time to develop. Numerous clinical studies have subsequently demonstrated that OKT3 can successfully reverse renal allograft rejection episodes in patients failing on conventional immunotherapy regimens.

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Section: Blocking Effect Of Okt3 On Established Killer Cellsmentioning

confidence: 99%