# MECHANISM OF NK MEDIATED CYTOLYSIS

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 1989 · $173,255

## Abstract

Natural killer (NK) cell mediated cytolysis can be resolved into
discrete stages of recognition, triggering, and lysis.  Little is
known concerning the molecular interactions involved in either of
these three stages.  We have isolated a monoclonal antibody
(MAb), 3E12, which blocks recognition of K-562 target cells by
NK effector cells.  This reagent blocks the formation of effector
cell-target cell conjugates, a necessary step required for the
subsequent lysis of target cells.  We propose to further
characterize this structure and catalogue its appearance on
putative targets cells in order to determine potential in vivo
targets of NK cells.  In addition to the development of this MAb,
we have developed antiidiotypic antibody to 3E12 in an attempt to
produce an antireceptor reagent which will react with the NK
effector cell receptor.  Several clones have been isolated which
react specifically with 3E12 and which significantly alter the
levels of NK cytotoxicity to K-562 target cells.  This antireceptor
reagent will be characterized and used to isolated and identify the
NK cell receptor.

We also propose additional studies on the mechanism of target
cell lysis by NK effector cells.  Special attention will be directed
to mechanisms of nuclear damage that are seen during NK
mediated cytolysis.  Preliminary data has shown that nuclear
damage is also a feature of cell damage mediated by soluble
mediators of NK cytolysis.  This will be further explored and
attempts will be made to identify a nuclease that we have found
in these soluble cytotoxic factors.  This proposal will attempt to
identify the source of this nuclease, effector cell or target cell,
to determine if cytotoxicity consists of directed destruction of
the target cell by factors from the effector cell or whether the
target cell contributes to its own demise due to a signal from the
effector cell which actives an internal disintegration message.

## Key facts

- **NIH application ID:** 3171412
- **Project number:** 5R01CA033589-06
- **Recipient organization:** VANDERBILT UNIVERSITY
- **SAM.gov UEI:** GTNBNWXJ12D5
- **Principal Investigator:** James Forbes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $173,255
- **Award type:** 5
- **Project period:** 1983-12-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171412

## Citation

> US National Institutes of Health, RePORTER application 3171412, MECHANISM OF NK MEDIATED CYTOLYSIS (5R01CA033589-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171412. Licensed CC0.

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