Masters Theses

Author

Steve Foster

Date of Award

8-1984

Degree Type

Thesis

Degree Name

Master of Science

Major

Microbiology

Major Professor

Carl J. Wust

Committee Members

Robert N. Moore, Albert T. Ichiki

Abstract

The pluripotent stem cell line, K-562, derived from a patient with chronic myelogenous leukemia in blastic crisis (46, 49, 50), is a commonly used target cell for studies of human natural killer (NK) cell activity. Sublines have been established from the original K-562 line, and have shown different phenotypic characteristics. These K-562 sublines were used in a study to examine possible variability in their susceptibility to NK-mediated lysis. Predominantly hypodiploid K-562 sublines, established early in passage of the parental line, were relatively resistant to lysis by NK, whereas hypotriploid lines were sensitive.

A cloned hypodiploid subline B1 V, was studied to characterize the basis for resistance to NK activity in hypodiploid K-562. Cells of this NK-resistant clone did not effectively compete with sensitive sublines in cold target inhibition assays, but were found to form conjugates with NK cells at levels similar to sensitive sublines. Furthermore this clone was susceptible to lysis by antibody-dependent cell-mediated mechanisms as well as by specific anti-K-562 serum plus complement. Together these data suggest that NK cells can recognize and bind to the resistant clone B1 V, but are not activated to mediate lysis.

The failure of B1 V targets to activate the NK cell lytic mechanism was independent of surface sialic acid. High salt extracts of B1 V did not inhibit lysis by NK cell as did those from NK-sensitive K-562 sublines. Thus, B1 V may lack surface protein determinants involved in the activation signal.

This study provides direct evidence for a target cell-associated signal for activation of the NK cell. This signal may represent an additional mode of regulation of NK activity in vivo.

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