Physiologically, T cell activation occurs upon recognition of processed antigen on the surface of an antigen-presenting cell in the context of proteins encoded by the major histocompatibility complex gene locus. The precise sequence of molecular events involved in T cell activation after T cell receptor triggering is unknown. It has been suspected for sometime, however, that additional molecules concerned with these processes may exist. Here we propose to characterize a murine cell surface molecule, provisionally termed sgp-60, defined by a hamster monoclonal antibody. Our preliminary data indicate that this molecule is novel, linked to the plasma membrane via a phosphatidylinositol anchor, and concerned with signaal transduction through the T cell antigen receptor/CD3 complex, This proposal aims at the detailed characterization of sgp-60 using immunological and biochemical methods. In particular, we propose to study its expression in lymphoid and non-lymphoid tissues, to determine the precise structure of sgp-60 including its primary amino acid sequence, and to clone the cDNA for the molecule. We will determine its role in T lymphocyte activation. We anticipate that the anti-sgp-60 antibody reagent will be a very useful tool to dissect early events in T cell activation. The preliminary data indicate that the antibody interferes with the increase in [Ca2+]i normally following T cell receptor stimulation. The use of this antibody will therefore allow us to directly test the significance of second messengers for the generation of biologic responses by T cells such as lymphokine production.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI030169-04
Application #
2065493
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1991-07-01
Project End
1996-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215