# STRUCTURE AND FUNCTION OF THE LYMPHOCYTE FC-E RECEPTOR

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 1993 · $252,254

## Abstract

DESCRIPTION (Investigator's  Abstract):  This is a continuation
application to study the molecular regulation, structure and function of
the low affinity IgE receptor (Fc-epsilon-RII), using  the mouse system.
The  overall aim is  to gain  further  insight  into the roles this
molecule plays in immediate hypersensitivity  and in B-cell activation
and differentiation.  In aim number 1 the molecular mechanism of IL-4
induced Fc-epsilon-RII up-regulation will be determined. The promoter
region of  the murine Fc-epsilon-RII  gene has  been tentatively
identified using  CAT reporter  plasmids.   This will be further defined
with additional deletion studies and the region  that responds to IL-4
will be determined.  The  mechanism will then be further explored by
analysis of DNA-binding proteins that may  interact with the  IL-4
responsive element. Finally, the  role that  mRNA stabilization  plays
in  the  IL-4- induced  Fc-epsilon-RII regulation  will also be
determined.  In aim number 2, the  Fc-epsilon-RII structure necessary for
IgE binding will be determined.   Current results indicate  that the Fc-
epsilon-RII forms a trimeric structure analogous to other "coiled-coil"
molecules such as tropomyosin.  The region responsible for this receptor-
receptor interaction  has been identified; it is termed the "stalk"
region of the Fc-epsilon-RII. Additional deletion  mutant Fc-epsilon-RII
as well  as chimeric Fc-epsilon-RII in which the  lectin homologous
region is attached to the other C-type family  "stalk" will be prepared
and analyzed for IgE- binding and oligomer formation.  A variety of new
biologic activities for the  sFc-epsilon-RII have been described in
humans.In aim  number 3 the soluble  Fc-epsilon-RII constructs prepared
in  aim number 2  will be analyzed for biologic activity.   The  sFc-
epsilon-RII constructs will be tested for activity against mast cells
with respect to  mediator and cytokine release and B-cells  with  respect
to costimulation,  IgE  production  and inhibition  of a proptosis.
These  studies will  also  allow the determination of  whether a ligand
other than IgE  exists for the Fc-epsilon-RII. Two biologic activities
for the intact  Fc-epsilon-RII  have been  identified  in the  current
grant period--enhancement  of  antigen  presentation  and  modification
of anti-Ig mediated  B-cell activation.  Using the mutant  Fc-epsilon-RII
molecules produced  in aim  number  2, the  correlation  between capacity
for  oligomer formation  and biologic  activity  will be  determined.In
addition,  these mutants, as well as a mutant Fc-epsilon-RII lacking a
cytoplasmic tail will be examined  for  the  capacity  to  modulate
internalization  and  cytoskeletal association.  Finally, as these
findings indicate new roles for IgE complexes, the effect of in  vivo
targeting the Fc-epsilon-RII on TH  phenotype will be assayed.

## Key facts

- **NIH application ID:** 3128112
- **Project number:** 2R01AI018697-13
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **SAM.gov UEI:** MLQFL4JSSAA9
- **Principal Investigator:** DANIEL H CONRAD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $252,254
- **Award type:** 2
- **Project period:** 1989-05-01 → 1997-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128112

## Citation

> US National Institutes of Health, RePORTER application 3128112, STRUCTURE AND FUNCTION OF THE LYMPHOCYTE FC-E RECEPTOR (2R01AI018697-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128112. Licensed CC0.

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