MHC-based reagents play an important role in the study of virus specific CD4 and CDS T cells. These reagents enable detection, characterization and purification of epitope-specific T cells by flow cytometry. With this application, research project Investigators propose studies that examine the roles of virus-specific CD4 and CDS T cells in immunopathogenesis of category A-C viral infections, and in vaccine induced immunity. The MHC Reagents Core will produce both MHC-I and II reagents for these studies. We will utilize established techniques for the expression and purification of MHC I and II molecules and will maintain inventories of these proteins in storage for generating peptide-MHC complexes as needed by Investigators for their studies. As peptide-MHC complexes are generated, they too will be placed in repository. These peptide-MHC complexes will largely be used to generate fluorochrome-labeled tetramers for studies involving flow cytometry. Analyses using novel techniques employing these reagents are being developed by the Technology Development Project. All complexed and multimerized reagents will undergo rigorous quality control testing using established column chromatography techniques and western blotting to detect properly folded molecules, and using flow cytometry to determine if cell lines with known specificities (provided by the Clinical Research Core) are appropriately labeled. As novel MHC I or II reagents are developed by the Technology Development Project, this Core will take over production at a late stage, when expression and re-folding protocols have been established. This Core will serve an important role for virtually all projects in this Program.

Public Health Relevance

The research projects in this program seek to define critical cellular immune responses to infections and immunizations that ultimately may be harnessed for designs of more effective preventive and therapeutic measures. For these studies, the MHC Reagents Core will produce reagents that have a proven record of revealing important information about cellular immune responses to infections and immunizations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI057319-09
Application #
8376592
Study Section
Special Emphasis Panel (ZAI1-KS-I)
Project Start
Project End
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
9
Fiscal Year
2012
Total Cost
$188,537
Indirect Cost
$70,668
Name
University of Massachusetts Medical School Worcester
Department
Type
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Mathew, Anuja (2017) Humanized mouse models to study human cell-mediated and humoral responses to dengue virus. Curr Opin Virol 25:76-80
Ramirez, Alejandro; Co, Mary; Mathew, Anuja (2016) CpG Improves Influenza Vaccine Efficacy in Young Adult but Not Aged Mice. PLoS One 11:e0150425
Townsley, E; O'Connor, G; Cosgrove, C et al. (2016) Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells. Clin Exp Immunol 183:419-30
Woda, Marcia; Friberg, Heather; Currier, Jeffrey R et al. (2016) Dynamics of Dengue Virus (DENV)-Specific B Cells in the Response to DENV Serotype 1 Infections, Using Flow Cytometry With Labeled Virions. J Infect Dis 214:1001-9
Tervo, Laura; Mäkelä, Satu; Syrjänen, Jaana et al. (2015) Smoking is associated with aggravated kidney injury in Puumala hantavirus-induced haemorrhagic fever with renal syndrome. Nephrol Dial Transplant 30:1693-8
Woda, Marcia; Mathew, Anuja (2015) Fluorescently labeled dengue viruses as probes to identify antigen-specific memory B cells by multiparametric flow cytometry. J Immunol Methods 416:167-77
Becerra-Artiles, Aniuska; Dominguez-Amorocho, Omar; Stern, Lawrence J et al. (2015) A Simple Proteomics-Based Approach to Identification of Immunodominant Antigens from a Complex Pathogen: Application to the CD4 T Cell Response against Human Herpesvirus 6B. PLoS One 10:e0142871
Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro et al. (2015) Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice. Exp Biol Med (Maywood) 240:67-78
Terajima, Masanori; Co, Mary Dawn T; Ennis, Francis A (2014) Age and different influenza viruses. Lancet Infect Dis 14:101
Mathew, Anuja; Townsley, Elizabeth; Ennis, Francis A (2014) Elucidating the role of T cells in protection against and pathogenesis of dengue virus infections. Future Microbiol 9:411-25

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