The TCR and Transgenic Mouse Development Core will use our expertise in creating animal models of CD4 T cells and human disease to develop state of the art systems to study the role of CD4 T cells during viral infections and detrimental immune-mediated pathology. Core 0 will have several objectives. First, in collaboration with Dr. Welsh, Project 1, we will determine the role of TCR-pMHC affinity in provoking activated CD4 T cells to be targeted by NK cells. With Dr. Swain, Project 2, we will produce and characterize a panel of CD4 T cells specific for influenza A (lAV). These T cells will be used to understand which CD4 T cells are activated during anti-viral immunity, and will also be used with Dr. Stern, Core B to identify novel viral epitopes and to aid in the development of virus-specific pMHC class II tetramers. lAV specific TCRs will be cloned and a novel set of transgenic mice expressing anti-viral TCRs will be created. These new virus-specific TCR Tg mice will be used by Projects 1, 2, and 3 to study anti-viral T cell responses. In collaboration with Dr. Swain and Dr Stern, we will evaluate the role of TCfR-pMIHC affinity in CD4 T cell lineage differentiation and function following lAV infection. We have extensive experience generating T cell hybridomas, cloning TCRs and producing TCR Tg mice. Additional experiments with Dr. Selin, Project 3, will identify mechanisms that cause of cross-reactive CDS T cells to become pathogenic. Experiments with Dr. Selin and Dr. Stern, Projects 3 and 4, will use our- TCR cloning methods and T cell expression systems to characterize human TCRs specific for lAV and HHV-6. The final objective of Core C is to minimize duplicate breeding programs by centralizing the breeding of TCR Tg mice.

Public Health Relevance

The T cell/TCR Core will provide essential molecular biology services to all of the Projects of the Program regarding the production of virus-specific T cell hybridomas, the cloning and characterization ofthe TCRs expressed on these T cell hybridomas. In addition, the Core will generate novel TCR Tg mice and maintain these and additional virus-specific TCR Tg mice used by all of the members of the Program. The services to be provided by the Core will be available to all Project Laboratories, and the Core will also be responsible for training personnel to perform assays.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-ZL-I (J1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Massachusetts Medical School Worcester
United States
Zip Code
Strutt, T M; Dhume, K; Finn, C M et al. (2018) IL-15 supports the generation of protective lung-resident memory CD4 T cells. Mucosal Immunol 11:668-680
Devarajan, Priyadharshini; Jones, Michael C; Kugler-Umana, Olivia et al. (2018) Pathogen Recognition by CD4 Effectors Drives Key Effector and Most Memory Cell Generation Against Respiratory Virus. Front Immunol 9:596
Hatfield, Steven D; Daniels, Keith A; O'Donnell, Carey L et al. (2018) Weak vaccinia virus-induced NK cell regulation of CD4 T cells is associated with reduced NK cell differentiation and cytolytic activity. Virology 519:131-144
Becerra-Artiles, Aniuska; Santoro, Tessa; Stern, Lawrence J (2018) Evaluation of a method to measure HHV-6B infection in vitro based on cell size. Virol J 15:4
Shin, Hyun Mu; Kapoor, Varun N; Kim, Gwanghun et al. (2017) Transient expression of ZBTB32 in anti-viral CD8+ T cells limits the magnitude of the effector response and the generation of memory. PLoS Pathog 13:e1006544
Song, InYoung; Gil, Anna; Mishra, Rabinarayan et al. (2017) Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope. Nat Struct Mol Biol 24:395-406
Watkin, Levi B; Mishra, Rabinarayan; Gil, Anna et al. (2017) Unique influenza A cross-reactive memory CD8 T-cell receptor repertoire has a potential to protect against EBV seroconversion. J Allergy Clin Immunol 140:1206-1210
Che, Jenny W; Daniels, Keith A; Selin, Liisa K et al. (2017) Heterologous Immunity and Persistent Murine Cytomegalovirus Infection. J Virol 91:
Rowe, Jared H; Stadinski, Brian D; Henderson, Lauren A et al. (2017) Abnormalities of T-cell receptor repertoire in CD4+ regulatory and conventional T cells in patients with RAG mutations: Implications for autoimmunity. J Allergy Clin Immunol 140:1739-1743.e7
Aslan, Nuray; Watkin, Levi B; Gil, Anna et al. (2017) Severity of Acute Infectious Mononucleosis Correlates with Cross-Reactive Influenza CD8 T-Cell Receptor Repertoires. MBio 8:

Showing the most recent 10 out of 41 publications