# PROTEINASES AND LETHAL MECHANISM OF NATURAL KILLER CELLS

> **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 1987 · $22,940

## Abstract

The lethal mechanism of lymphocyte-mediated cytotoxicity of tumor cells is
unknown.  Specific irreversible inhibitors, e.g., alpha-1-antichymotrypsin
and haptenic active site reactants, were instrumental to our initial,
indirect approaches that indicate that a serine proteinase with aromatic
amino acid specificity must have a crucial role in human, natural killer
(NK) lymphocyte-mediated cytotoxicity.  We will use these inhibitors to tag
NK-associated proteinases for subsequent antibody affinity isolation.  The
Mr, subunit structure, pI, and cellular localization of the isolated
NK-associated proteinase(s) will be determined.

NK cell lines and clones have been established.  These and additional NK
clones will be maintained as the source of material for these studies.
Major emphasis will be placed on obtaining IL-2-independent killer clones.
This will be done by creating hybridomas with HAT-sensitive cell lines by
transformation and by mutation.

The NK proteinase may function in NK-associated degranulation, in
activation of a lethal substance, or in yet unrecognized processes.  We
will assess the importance of degranulation in NK and the potential
proteinase control of degranulation.  In addition, we will examine whether
prolethal substances are cleaved prior to transfer of lethal materials to
the tumor cells destined to die.  Because of their experimental
accessibility, the proteinases that control cytotoxicity could be the first
components of the lymphocytes' lethal weaponry to be isolated.  (LB)

## Key facts

- **NIH application ID:** 3177448
- **Project number:** 3R01CA038942-03S1
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **SAM.gov UEI:** WLDGTNCFFJZ3
- **Principal Investigator:** Dorothy Hudig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $22,940
- **Award type:** 3
- **Project period:** 1984-05-11 → 1988-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177448

## Citation

> US National Institutes of Health, RePORTER application 3177448, PROTEINASES AND LETHAL MECHANISM OF NATURAL KILLER CELLS (3R01CA038942-03S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177448. Licensed CC0.

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