BIOLOGICAL FUNCTION OF T LYMPHOCYTE SURFACE PROTEINS

Project: Research project

Description

The activation of T lymphocytes is dependent upon the function of
a number of cell surface proteins on T cells. A monoclonal
antibody has been prepared to a non-polymorphic epitope on Ly-6
molecules, and this antibody is mitogenic for T lymphocytes. This
observation strongly implicates Ly-6 molecules in participating in
the initial signalling that results in activation of T lymphocytes.
The experiments in this proposal will use this mitogenic anti-Ly-6
monoclonal antibody to define the mechanism by which Ly-6
molecules function to regulate T cell responses in vitro and to
determine whether Ly-6 molecules function as an alternative
pathway of murine T cell activation. The role of non-T accessory
cells for polyclonal Ly-6 mediated T cell activation will be
defined in part by comparing the capacity of different viable and
paraformaldehyde fixed normal and tumor cell populations, and
their isolated membranes, to provide the requisite accessory cell
signals. We will also evaluate by limiting dilution analysis
whether the capacity of anti-Ly-6 antibody to markedly augment
specific T cell responses is due to the stimulation of increased
numbers of antigen-specific T cells or is due to enhancement of
antigen non-specific factors that are required for T cell clonal
expansion. By cellular and genetic studies, we will determine the
basis that accounts for the failure of T lymphocytes from A/J
mice to be polyclonally activated via Ly-6 molecules. The
capacity of lymphokines to regulate Ly-6 molecules will be
characterized in vitro and the potential effect on lymphocyte
function will be assessed, especially to obtain evidence of whether
Ly-6 molecules may also be functional in B lymphocytes. Other
investigations will be concerned with whether expression of Ly-6
molecules on T cells correlates with a unique stage of T cell
differentiation, i.e. IL-2 secretion by helper cells. The studies are
relevant to understanding the physiological function of Ly-6
molecules and to provide a new model with which to study the
complex cellular and molecular interactions that are necessary to
cause T cell activation. In view of the capacity of activation of T
cells by Ly-6 molecules to increase antigen-specific responses,
these studies are also relevant to development of strategies that
may lead to enhanced immune function in patients with
immunodeficiency diseases, e.g. AIDS.
StatusFinished
Effective start/end date9/1/878/31/96

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $154,527.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $166,922.00
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Isoantigens
T-Lymphocytes
Interleukin-2
Membrane Proteins
B-Lymphocytes
CD3 Antigens
Hybridomas
Autoimmunity
Immune System
Proteins
Complementary DNA
Immunoglobulins
Ligands
Phenotype
Neoplasms
Antibodies
TCF Transcription Factors
Antigens

ASJC

  • Medicine(all)