# STRUCTURE-FUNCTION RELATIONSHIPS OF IMMUNORECEPTORS

> **NIH NIH R01** · CORNELL UNIVERSITY · 1993 · $233,167

## Abstract

The structure and cell surface dynamics of two different immunoreceptors,
the high affinity receptor for IgE (Fc epsilon-Rl) and the T cell
receptor for antigen (TCR), will be investigated in a continuing effort
to elucidate the molecular details of how these complex proteins function
to initiate a cascade of intracellular events in response to foreign
antigen.  Fluorescence resonance energy transfer will be used to map the
spatial relationships among subunits within TCR and between this receptor
and other proteins with which it interacts.  These studies will include
the development of novel energy transfer probes based on genetically
engineered, covalently coupled heavy and light chain variable domains
from monoclonal anti-receptor antibodies to obtain more precise distance
information.  Previous energy transfer measurements showed the
conformation of IgE to be bent, and this structure will be further
characterized with electron microscopy.  Chimeric murine IgE/ human IgG1
antibodies will be used to identify the sequences involved in maintaining
the bent conformation, and computational methods will be employed to
assess the conformation of the segment of seven amino acids at the
proposed site of bending and interaction with Fc epsilon-RI.  Biochemical
methods will be used to characterize proteins that interact with the
IgE-receptor complex and are captured by chemical crosslinking.
Efficient cell-cell fusion will be exploited as a method for
investigating receptor function with both mutant and native receptors.
Phosphorescence anisotropy decay measurements of monomeric and dimeric
IgE-receptor complexes will be continued to investigate the structural
interactions resulting in the reduced rotational diffusion observed for
dimers; wildtype Fc epsilon-RI will be compared to mutants with
cytoplasmic tail deletions and to chimeric constructs of the alpha
subunit, and anti-Fc epsilon-RI monoclonal antibodies will be used to
directly assess the influence of bound IgE on the receptor mobility
properties.  The dynamics of TCR on the cell surface will also be
characterized with measurements of fluorescence photobleaching recovery,
phosphorescence anisotropy decay, and quantitative video microscopy.
Mutant forms of the TCR will be examined to see whether TCR dynamics play
an important role in its functional interactions with histocompatibility
antigens on target cells.

## Key facts

- **NIH application ID:** 3127824
- **Project number:** 2R01AI018306-12A1
- **Recipient organization:** CORNELL UNIVERSITY
- **SAM.gov UEI:** G56PUALJ3KT5
- **Principal Investigator:** Barbara A Baird
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $233,167
- **Award type:** 2
- **Project period:** 1981-08-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127824

## Citation

> US National Institutes of Health, RePORTER application 3127824, STRUCTURE-FUNCTION RELATIONSHIPS OF IMMUNORECEPTORS (2R01AI018306-12A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127824. Licensed CC0.

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