Core B, the Antibody / Ig Fusion Core, will coordinate the use of mAb and Ig fusion proteins for the study of the roles of pathways in the B7:CD28 superfamily in regulating T cell activation and tolerance in vivo, so that these reagents are an easily accessible means of addressing the functions of these important immunoregulatory pathways in vivo. Core B will serve as a critical means by which the Costimulation PPG will achieve its goals of understanding the in vivo functions of the negative second signals provided by pathways in the B7:CD28 family individually, the interactions among these negative signals, and the balance between stimulatory and inhibitory signals transmitted by pathways within the B7:CD28 superfamily. The major goals of Core B, the Antibody / Ig Fusion Core, are to generate novel reagents that facilitate the analysis of the expression and function of B7:CD28 family members and to serve as a repository for and provide existing reagents for the Costimulation PPG Projects and Core C. The generation of novel reagents that induce negative signals is central to the mission of the Costimulation PPG, and Core B provides a critical means by which the PPG will achieve this goal. The availability of large quantities of Ig fusion proteins and mAbs is critical to the success of Projects 1-5. Ig fusion proteins will be used for expression, functional, and signaling studies. Ig fusion proteins, via binding to their ligand, will visualize ligand-expressing cells and may act as agonists via cross-linking and transducing signals through receptors. In addition, Ig fusion proteins may serve as a means to specifically block receptor/ligand interactions. MAbs also will be used to visualize the expression of B7:CD28 family members and as pathway agonists and antagonists. To accomplish these goals, Core B has two aims:
Specific Aim 1 : To generate novel monoclonal antibodies to study the function and expression of B7:CD28 family members and their polymorphic variants.
Specific Aim 2 : To serve as a repository and maintain and produce existing and newly generated 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

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI056299-09
Application #
8379893
Study Section
Special Emphasis Panel (ZAI1-RJ-I)
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
9
Fiscal Year
2012
Total Cost
$308,842
Indirect Cost
$51,447
Name
Harvard University
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
MacDonald, Kelli Pa; Blazar, Bruce R; Hill, Geoffrey R (2017) Cytokine mediators of chronic graft-versus-host disease. J Clin Invest 127:2452-2463
Moffett, Howell F; Cartwright, Adam N R; Kim, Hye-Jung et al. (2017) The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection. Nat Immunol 18:791-799
Kamphorst, Alice O; Wieland, Andreas; Nasti, Tahseen et al. (2017) Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science 355:1423-1427
Guo, Yanxia; Walsh, Alice M; Fearon, Ursula et al. (2017) CD40L-Dependent Pathway Is Active at Various Stages of Rheumatoid Arthritis Disease Progression. J Immunol 198:4490-4501
MacDonald, Kelli P A; Hill, Geoffrey R; Blazar, Bruce R (2017) Chronic graft-versus-host disease: biological insights from preclinical and clinical studies. Blood 129:13-21
Rigas, Diamanda; Lewis, Gavin; Aron, Jennifer L et al. (2017) Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction. J Allergy Clin Immunol 139:1468-1477.e2
Juneja, Vikram R; McGuire, Kathleen A; Manguso, Robert T et al. (2017) PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J Exp Med 214:895-904
Zhang, Ruan; Sage, Peter T; Finn, Kelsey et al. (2017) B Cells Drive Autoimmunity in Mice with CD28-Deficient Regulatory T Cells. J Immunol 199:3972-3980
Hippen, K L; O'Connor, R S; Lemire, A M et al. (2017) In Vitro Induction of Human Regulatory T Cells Using Conditions of Low Tryptophan Plus Kynurenines. Am J Transplant 17:3098-3113
Du, Jing; Paz, Katelyn; Flynn, Ryan et al. (2017) Pirfenidone ameliorates murine chronic GVHD through inhibition of macrophage infiltration and TGF-? production. Blood 129:2570-2580

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