The Scientific Core (Core B), will coordinate the use of mAbs and Ig fusion proteins for studying the expression and function of TIM proteins in T cell activation and tolerance. These reagents will be an easily accessible means of addressing the functions of these important immunoregulatory pathways. The major goals of the Scientific Core are to generate novel reagents that facilitate the analysis of the expression and function of TIM family members and to serve as a repository for and provide existing reagents for the PPG Projects. The availability of large quantities of mAbs and Ig fusion proteins Is critical to the success of Projects 1-4. MAbs will be used to visualize the expression of TIM family members and as pathway agonists and antagonists. Ig fusion proteins will be used for expression, function, and signaling studies. In addition, Ig fusion proteins may serve as a means to specifically block receptor/ligand interactions. To accomplish these goals, the Scientific Core has two aims:
Specific Aim 1 : To generate novel monoclonal antibodies and Ig fusion proteins to study the function and expression of TIM family members.
Specific Aim 2 : To serve as a repository and maintain and produce existing and newly generated TIM mAbs and Ig fusion proteins for PPG investigators. The production of these critical reagents by a core not only will be time and cost efficient, but also provide standardized reagents that will facilitate comparison of data by Investigators in this PPG.

Public Health Relevance

The TIM pathway regulates immune responses and is involved in the development of asthma and autoimmune diseases. Core B will make reagents to (1) see where TIMs are expressed;(2) block the pathway;(3) activate the pathway, thereby understanding how best to regulate the immune response.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01AI054456-11
Application #
8866348
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02215
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Angiari, Stefano; Donnarumma, Tiziano; Rossi, Barbara et al. (2014) TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T cell trafficking during inflammation and autoimmunity. Immunity 40:542-53
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Manangeeswaran, Mohanraj; Jacques, Jerome; Tami, Cecilia et al. (2012) Binding of hepatitis A virus to its cellular receptor 1 inhibits T-regulatory cell functions in humans. Gastroenterology 142:1516-25.e3
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