Title

Functional characterization of CD30 on the large granular lymphoma cell line YT, and the cloning of a murine CD30cDNA homologue

Date of Award

1993

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

First Committee Member

Eckhard R. Podack, Committee Chair

Abstract

Natural killer (NK) cells are large granular lymphocytes (LGL) that have the ability to lyse certain tumor and virally infected cells without prior sensitization. Although several receptors have been shown to participate in the recognition and the triggering of tumor cell lysis, the putative NK receptor, if it does exist, has not been conclusively demonstrated. To identify cell surface molecules that are involved in recognition and triggering, monoclonal antibodies were made against the human LGL lymphoma cell line YT. Antibodies were screened for their ability to affect the cytotoxicity of YT cells against Raji target cells. The monoclonal antibody chosen for the basis of this study, C10, downregulated cytotoxicity and induced homotypic aggregation of YT cells in a time dependent manner. Both processes required prolonged pretreatment of YT cells to observe the effect. C10 was shown to recognize CD30, which was originally described as the Ki-1 antigen expressed by Reed-Sternberg cells of Hodgkin's lymphoma. Studies revealed that C10, upon binding to CD30, had indirect effects on cytotoxicity and aggregation by causing the downregulation of CD28 expression and the upregulation (of expression or affinity) of an unidentified adhesion molecule. Since CD28 expression on YT cells is required for the recognition and lysis of B7 expressing targets such as Raji, it is suggested that C10 inhibition of cytotoxicity is caused by the downregulation of CD28 expression or signaling. Anti-CD30 also caused the upregulation of IL-2R p55 expression. During the course of this study, the murine homologue of CD30 was cloned and found to be expressed on activated lymphocytes and in the thymus. Comparison of the peptide structure of murine and human CD30 revealed that the murine peptide has a portion of the extracellular domain deleted. These studies suggest an important role for CD30 in lymphocyte activation and development.

Keywords

Biology, Molecular; Health Sciences, Immunology

Link to Full Text

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