# MECHANISM OF LYMPHOCYTE ACTIVATION BY THIOL COMPOUNDS

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1993 · $268,330

## Abstract

DESCRIPTION (Adapted from applicant's abstract):  Experiments have been
designed to study the interactions between cellular components and a
unique, intracellular class of lymphocyte stimulator, the 7,8-disubstituted
guanine ribonucleosides.  While encouraging results with these compounds in
studies of cells from patients with Common Variable Immunodeficiency, IgA
deficiency, AIDS-related complex and AIDS suggest that they may have
significant clinical potential, little is known about their mechanism of
action.  The first major objective proposed is to evaluate the biological
relevance of the binding proteins as receptors.  The relevance of proteins
radiolabeled by biologically active photoaffinity ligands will be
determined in competition studies, and by examining hyporesponsive,
nonresponsive, and inducible cell types.  Monoclonal antibodies to these
proteins will be raised and their specificity verified by Western blot.
These antibodies will be micro-injected into cells to antagonize or trigger
biological responses.  Purified receptor proteins will be used to
reconstitute nucleoside responsiveness in hyporesponsive, nonresponsive,
and inducible cells.  Affinity-purified proteins from normal mice will be
examined for binding affinity and binding site topology, and compared with
proteins from hyporesponsive and nonresponsive strains.  The second major
objective is to determine the physico-chemical properties of purified
(receptor) proteins, including Mr, isoelectric point, degree of
glycosylation and linkages involved.  The relationship between the two
forms of binding protein will be explored in cells from normal and
hyporesponsive strains.  Proteolytic cleavage fragments will be separated
and microsequenced to elucidate the overall protein sequences.  The third
major objective is to study interactions between the nucleoside and its
receptor.  The functional topology of ligand recognition by the receptor
will be studied for high and low affinity receptors with an array of
biologically inactive analogs.  Similarly, binding domains on the receptor
proteins will be defined.  Finally, nucleoside receptors will be
investigated within the context of the cell.  Immuno-localization of
receptors in resting and activated cells, translocation to different
cellular compartments, cycling, and degradation will be studied with the
electron microscope.  Regulation of receptor synthesis and turnover will be
compared to functional status.  Effects of B cell agonists and lymphokines
on receptor expression will be examined throughout the cell cycle in
responder, nonresponder and inducible cell types.

## Key facts

- **NIH application ID:** 3126133
- **Project number:** 5R01AI015284-15
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **SAM.gov UEI:** PHZJFZ32NKH4
- **Principal Investigator:** MICHAEL G GOODMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $268,330
- **Award type:** 5
- **Project period:** 1978-08-01 → 1995-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126133

## Citation

> US National Institutes of Health, RePORTER application 3126133, MECHANISM OF LYMPHOCYTE ACTIVATION BY THIOL COMPOUNDS (5R01AI015284-15). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126133. Licensed CC0.

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