# BIOLOGY OF HUMAN T CELL ACTIVATION

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 1988 · $72,856

## Abstract

We propose to study the mechanisms of activation of human T
cells.  We will focus on the study of the early events that follow
binding of ligands that lead to interleukin 2 receptor (IL2r)
expression and on the study of the nature of the interactions
between T cells and monocytes that lead to IL2 synthesis and
proliferation.

The role of GTP binding (G) proteins in signal transduction that
leads to the activation of phospholipase C (PLC), turnover of
inositol phospholipids (Pt Ins) and translocation of protein kinase
C (PKC) will be examined in T cells stimulated with anti CD3
monoclonal antibodies (mAb).  A defect in T cell receptor coupled
G protein will be ascertained in a patient with a signal
transduction defect.  Assays for G protein enhanced activation of
PLC in cell membranes and reconstitution experiments on cell
lines from the patient with signal transduction defect will be used
to monitor the purification of receptor/CD3 coupled G protein
from normal lymphocytes.  We will study the role of Pt Ins, PKC
activation, CD3 phosphorylation and rise in intracellular calcium
(Ca++)i in different pathways of T cell activation.  The
relationship between the generation of the Pt Ins breakdown
product inositol (1,4,5) triphosphate (IP3) and (Ca++)i  rise will be
examined in resting T cells stimulated with CD3 mAb.

We will test the hypothesis that cell-cell interaction between
ligand activated T cells and monocytes is necessary to induce IL1
responsiveness in T cells leading to IL2 synthesis.  We will
examine the role of LFA1 molecules in T cell  activation, attempt
to identify LFA1 receptors by raising the mAb to Epstein-Barr
transformed B cells from LFA1 deficient patients and study the
mechanism of LFA1-LFA1 receptor interaction.  The role of these
interactions in inducing IL1 responsiveness in T cells will be
studied, and we will examine whether this responsiveness is due to
induction of IL1 receptors, and results in IL2 synthesis allowing
proliferation to proceed.

The basic significance of this work is to define the events and
pathways that lead to the elicitation of T cell mediated immunity.
The results of the proposed studies will be applicable to the
understanding and treatment of immunodeficiencies, autoimmune
diseases and transplantation.

## Key facts

- **NIH application ID:** 3129992
- **Project number:** 5R01AI020373-05
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **SAM.gov UEI:** Z1L9F1MM1RY3
- **Principal Investigator:** RAIF SALIM GEHA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $72,856
- **Award type:** 5
- **Project period:** 1983-09-01 → 1989-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129992

## Citation

> US National Institutes of Health, RePORTER application 3129992, BIOLOGY OF HUMAN T CELL ACTIVATION (5R01AI020373-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129992. Licensed CC0.

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