# ANALYSIS OF HUMAN NK FUNCTION

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1987 · $167,244

## Abstract

The major histocompatibility complex (MHC) plays a key role in
regulating the immune response, but MHC molecules may also
have a more generalized role in a variety of cellular functions.
MHC molecules associate with cell surface molecules involved in
cell growth and also share many physical characteristics with
receptor molecules.  It is thus likely that MHC molecules may
have receptor functions as well.

This proposal focuses on two additional functions of MHC
molecules that we recently described:  the regulation of the
cytolytic activity of human natural killer (NK) cells, and a role in
the activation and proliferation of human T and B lymphocytes
and NK cells.  The major goal of this project is to determine the
mechanism by which MHC cell surface molecules affect both
cytolytic activity and lymphocyte growth and activation.

Monoclonal antibodies (mAbs) with specificity for HLA class I and
class II molecules were generated which affect the lytic activity
of a cloned line of human NK cells (NK 3.3).  The HLA class I-
specific mAb that augments lysis (mAb 131) has been
characterized as a unique anti-HLA-A locus-specific mAb.  In
contrast, an anti-HLA-B locus-specific mAb (4E) inhibits killing,
suggesting HLA class I-locus-specific effects on NK function.
Similarly, the anti-HLA-A and anti-HLA-B locus-specific mAbs
have differential effects on the activation of T and B lymphocytes
by a variety of mitogens.  Such functional differences in HLA-A
and B locus-encoded gene products have not been previously
described.  These mAbs are thus valuable tools for understanding
the role of MHC molecules in lymphocyte functions.  The working
hypothesis is:  1) MHC molecules associate with functionally
important receptors in the membranes of NK cells, T cells and B
cells, and 2) HLA-A locus and B locus gene products form
different associations resulting in different functional effects of
the antibodies directed against them.  We will test this hypothesis
by:  1) examining potential physical associations of MHC class I A
and B locus-encoded molecules with other functionally important
molecules on NK, T and B cells, 2) studying differential recycling
and phosphorylation of MHC molecules in these cells, and 3)
studying changes in early metabolic events and gene expression
associated with activation or lytic activity in NK, T and B cells in
the absence and presence of the anti-HLA and B locus-specific
mAbs.  These studies will provide further information on the role
of the MHC in cellular functions, including growth, and provide
greater insight into the mechanisms and regulation of lytic
function and cellular proliferation.

## Key facts

- **NIH application ID:** 3175678
- **Project number:** 2R01CA037827-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** JACKI KORNBLUTH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $167,244
- **Award type:** 2
- **Project period:** 1984-07-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175678

## Citation

> US National Institutes of Health, RePORTER application 3175678, ANALYSIS OF HUMAN NK FUNCTION (2R01CA037827-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175678. Licensed CC0.

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