# TARGET CELL LYSIS BY CYTOLYTIC EFFECTOR CELLS

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 1987 · $166,882

## Abstract

The objective of this proposal is to analyze the events that lead to target
cell lysis by cloned killer cells from mice.  Previous experiments with
cloned murine natural killer (NK) cells had shown that subsequent to an
apparently random binding of NK cells to their targets, a repositioning of
the microtubule organizing center (MTOC) and Golgi apparatus (GA) toward
the target-binding site occurs.  Next, granules migrate to the
target-binding site and give rise to vesicles that carry cytolytic
molecules to the target membrane.  The present proposal's aim is to analyze
the cytolytic killing by NK cells and by specific T-killer cells.  The
project focuses on three individual questions:  (1) Is there GA-MTOC
reorientation in T-killer cells and what are the signals that induce
reorientation and granular traffic to the target-binding site?; (2) Is it
possible to demonstrate that cytolytic molecules are generated in the
granules of killer cells and can granules be induced in a cell-free system
to lyse targets, assemble cytolytic vesicles and cytolytic molecules?; and
(3) Can the putative cytolytic molecules be purified and characterized in
order to test their function in a cell-free system?  An attempt will be
made to purify and characterize the putative cytolytic molecules in order
to test their function in a cell-free system.  Cloned cell lines will be
used for most experiments.  Intracellular organelles will be visualized by
fluoresceinated-specific antibody.  Granules will be isolated by percoll
gradient centrifugation and their function and protein composition
analyzed.  Cytolytic tubular complexes will be isolated by detergent
solubilization followed by gel filtration.  Their subunit structure will be
analyzed and antibodies specific for the complexes will be raised and used
for functional and biochemical analysis.  (SR)

## Key facts

- **NIH application ID:** 3178837
- **Project number:** 5R01CA039623-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **SAM.gov UEI:** G88KLJR3KYT5
- **Principal Investigator:** GUNTHER DENNERT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $166,882
- **Award type:** 5
- **Project period:** 1985-07-01 → 1988-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178837

## Citation

> US National Institutes of Health, RePORTER application 3178837, TARGET CELL LYSIS BY CYTOLYTIC EFFECTOR CELLS (5R01CA039623-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178837. Licensed CC0.

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