# STUDIES ON DIPHTHERIA TOXIN AND ITS RECEPTOR

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1987 · $149,431

## Abstract

Diphtheria is the prototype of an exotoxin-mediated infectious disease.
Diphtheria toxin acts on toxin-sensitive cells by:  1) binding, via its
B-fragment, to specific cell surface receptors, 2) translocation of the
A-fragment into the cytoplasm, and 3) inhibition of protein synthesis by
the fragment A-catalyzed ADP-ribosylation of elongation factor 2.  The
overall objective of this proposal is to characterize the receptor-binding
domain(s) of the toxin molecule, and to fully characterize the specific
diphtheria toxin-binding cell surface glycoproteins and their toxin-binding
domain(s).  The diphtheria toxin-binding glycoproteins are detected
utilizing a glycoprotein-enriched fraction prepared from exogenously
radiolabeled cells, followed by immunoprecipitation with diphtheria toxin
plus antiserum to diphtheria toxin.  By this method one major diphtheria
toxin-binding glycoprotein is detected in hamster thymocytes while various
(up to five) diphtheria toxin-binding glycoproteins are detected on the
cell surface of toxin-sensitive cells grown in tissue culture (e.g. Vero,
baby hamster kidney and Chinese hamster ovary cells).  The nature of this
multiple diphtheria toxin-binding glycoproteins will be investigated by
both biochemical and immunological approaches.  Specific monoclonal
antibodies will be prepared against each of these glycoproteins and will be
tested for their protective effect against toxin-mediated cytotoxicity in
order to determine which one of the diphtheria toxin-binding glycoproteins
represents the true physiological toxin receptor on cells.  These
antibodies will also be utilized to investigate the cell surface
distribution and the internalization mechanism of the diphtheria
toxin-binding glycoproteins.  The results of this proposed research will
significantly extend our knowledge of diphtheria toxin: receptor
interactions and will further our understanding of the mechanisms involved
in receptor-mediated internalization of such macromolecules as hormones,
growth factors, and other exotoxins.

## Key facts

- **NIH application ID:** 3126850
- **Project number:** 5R01AI016805-08
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** LEON EIDELS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $149,431
- **Award type:** 5
- **Project period:** 1980-04-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126850

## Citation

> US National Institutes of Health, RePORTER application 3126850, STUDIES ON DIPHTHERIA TOXIN AND ITS RECEPTOR (5R01AI016805-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126850. Licensed CC0.

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