# GENERATION AND EXPRESSION OF CYTOTOXIC T CELL FUNCTION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1989 · $5,747

## Abstract

The experiments in the present application are directed toward resolving:
1.)  The mechanism of CTL-mediated lysis.  The mechanism by which cytotoxic
T lymphocytes kill specific target cells in still unknown.  A study of
lysis in lectin-mediated cytolysis (LDCC) led us to propose a new mechanism
for CTL-mediated cytolysis, in which target cell death occurs as a result
of distortion of target cell MHC proteins.  Leakage at the interface
between the transmembrane MHC proteins and surrounding lipids is postulated
to lead to irreversible osmotic damage.  Experiments are included in this
proposal to test our hypothesis.  Antibodies to MHC proteins, other
transmembrane proteins, non-transmembrane proteins, and purely lipid
antigens will be coupled to the surface of inert microspheres, microtiter
wells, RBC or other nonlytic cell types.  These will then be incubated with
51Cr-labeled target cells, and the rate of 51Cr release monitored.  2.)
The relationship of lectin-mediated polyclonal activation of CTL function
to LDCC and to antigen activation of CTL function.  Certain plant lectins
have been used both to activate (CTL function, and to mediate lysis in
cases where MHC-restricted recognition is presumed not to occur.  We have
recently shown that target cell lysis in LDCC is in fact MHC-restricted,
and we have obtained preliminary data indicating that lectin-mediated,
polyclonal generation of CTL function is also controlled by MHC proteins
involved in lectin presentation.  We propose experiments to explore this
point further, and to analyze its significance for CTL function generally.
Using specific MHC antibodies, appropriate H-2 recombinant and congenic
strains, and MHC positive and negative cell lines, we will probe the
involvement of MHC proteins in activation of CTL function in primary and
secondary reactions, in both syngeneic and allogeneic combination.  We will
also clone out individual CTL generated by lectin and compare their
properties will CTL generated by specific antigen.

## Key facts

- **NIH application ID:** 3125847
- **Project number:** 3R01AI014747-16S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **SAM.gov UEI:** RN64EPNH8JC6
- **Principal Investigator:** WILLIAM R CLARK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $5,747
- **Award type:** 3
- **Project period:** 1978-09-30 → 1990-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125847

## Citation

> US National Institutes of Health, RePORTER application 3125847, GENERATION AND EXPRESSION OF CYTOTOXIC T CELL FUNCTION (3R01AI014747-16S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125847. Licensed CC0.

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