# HUMAN T CELL ANTIGEN RECOGNITION STRUCTURES

> **NIH NIH R01** · DANA-FARBER CANCER INST · 1992 · $276,116

## Abstract

The receptor for antigen and MHC (T3-Ti) on the vast majority of
human T lymphocytes is a molecular complex comprised of an
immunoglobulin-like Ti alpha-beta disulfide-linked heterodimer
and three non-covalently associated monomorphic subunits (T3
gamma, T3 delta and T3 epsilon).  Although much is known about
the molecular nature of Ti diversity encoded by V, D and J-like
elements and the primary structures of individual T3 subunits, the
signal transduction process is ill-defined.  Its molecular basis will
be the subject of the present proposal.  Firstly, monoclonal
antibodies will be produced to the native external domain of
individual T3 subunits expressed in the baculoviral system.  These
reagents will allow us to determine whether there are unique
functional effects attributable to a given subunit.  Alterations in
(Ca2+)i, phosphoinositide turnover, phosphorylation events and
gene transcription will be examined after external domain
perturbation.  Furthermore, novel strategies for developing
antibodies to other putative T3-Ti associated surface structures
will be devised and their primary structure analyzed by
microsequencing and cDNA cloning.  Secondly, through the use of
gene transfer techniques and truncation mutants, the signal
transduction function of individual cytoplasmic domains of T3
gamma, T3 delta and T3 epsilon will be defined.  The role of
potential phosphorylation sites in the cytoplasmic domain will be
examined via site directed mutagenesis.  The significance of the
single acidic amino acid residue in the transmembrane segment of
each T3 subunit with respect to T3-Ti stability and function will
be investigated.  Expression of T3-Ti subunit RNAs in xenopus
oocytes will be attempted with the view of coupling T3-Ti
complex signalling to the endogenous oocyte IP3 triggered C1-
channel as a rapid assay for receptor mediated activation events.
Thirdly, the role of the T3-Ti subunits in signalling growth
inhibition will be characterized.  It will be determined whether
anti-T3 modulation functionally uncouples the T3-Ti complex
from a G protein, inhibits protein kinase C or induces an arrestin-
like protein to bind the T3-Ti complex.  This desensitization
response will be studied in detail with Jurkat mutants which have
cytoplasmic deletions of individual T3 subunits.  Finally, as the
binding of the LFA-3 molecule to the CD2 external domain
appears to amplify triggering through the T3-Ti complex, we will
determine whether the T3 subunits are modified by
phosphorylation or new protein associations after such an
interaction.

## Key facts

- **NIH application ID:** 3129240
- **Project number:** 5R01AI019807-10
- **Recipient organization:** DANA-FARBER CANCER INST
- **SAM.gov UEI:** DPMGH9MG1X67
- **Principal Investigator:** ELLIS L REINHERZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $276,116
- **Award type:** 5
- **Project period:** 1983-05-01 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129240

## Citation

> US National Institutes of Health, RePORTER application 3129240, HUMAN T CELL ANTIGEN RECOGNITION STRUCTURES (5R01AI019807-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129240. Licensed CC0.

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