# KILLER CELL SURFACE ANTIGENS:  BIOCHEMISTRY AND FUNCTION

> **NIH NIH R01** · DONALD GUTHRIE FOUNDATION · 1987 · $92,125

## Abstract

Natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) and mononuclear
phagocytes represent three major systems of cell-mediated cytotoxicity
against tumors.  In order to dissect cell surface events important in the
cytolytic mechanism, monoclonal antibodies (MABs) against killer cell
surfaces have been screened for the ability to block cell-mediated
cytotoxicity in the absence of complement.  One MAB (RH1-38) specifically
blocks cytotoxicity mediated by at least three different effector cells,
including NK cells, CTLs, and a monocyte-like cell (phorbal myristate
acetate-stimulated HL-60).  The antibody immunoprecipitates from
PMS-stimulated HL-60 a bimolecular complex (195,000 and 125,000 daltons)
which is biochemically similar to the LFA-1 antigen, a previously described
cell surface antigen found on CTLs.  However, RH1-38, unlike previously
described anti-LFA-1  antibodies,  does not  inhibit effector-target
binding.  In addition, kinetic studies and single cell cytotoxicity assays
have demonstrated that RH1-38 blocks a late step in the cytolytic
mechanism.  Thus, RH1-38 recognizes either a functionally different epitope
on the LFA-1 molecule or alternatively a distinct, functionally important
cell surface molecule.

Using already developed techniques to determine molecular weight, subunit
structure, and surface antigen density, the principal investigator proposes
to test the hypothesis that differences in molecular structure and/or
surface antigen density are related to cytotoxic activity.  In addition,
using the HL-60 cell line as a source of antigen, the molecule recognized
by RH1-38 will be further characterized biochemically.  A variety of other,
noncytotoxic immunologic functions will be examined with respect to
inhibition by this monoclonal antibody, in order to survey its effect on
the immune response.  As time permits, it is further proposed to:  1)
examine molecular structure and antigen density on lymphocytes from select
NK-deficient disease states; 2) develop methods to insert the antigen into
the surface on noncytotoxic cells using antigen reconstituted into
phosphatidyl choline vesicles; and 3) develop methods for exogenous
cell-free translation of the mRNA that encodes for the relevant antigen.

Characterization of this and other MABs and the functionally important cell
surface molecules they recognize is likely to yield complementary
information leading to a dissection of cell surface events important in the
cytotoxic response.  This will lead to a better understanding of host
defense against infectious and malignant disease.  (CS)

## Key facts

- **NIH application ID:** 3174707
- **Project number:** 7R01CA037026-04
- **Recipient organization:** DONALD GUTHRIE FOUNDATION
- **SAM.gov UEI:** EQN2T77767Y3
- **Principal Investigator:** ROBERT E HALL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $92,125
- **Award type:** 7
- **Project period:** 1987-08-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174707

## Citation

> US National Institutes of Health, RePORTER application 3174707, KILLER CELL SURFACE ANTIGENS:  BIOCHEMISTRY AND FUNCTION (7R01CA037026-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174707. Licensed CC0.

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