Abstract

EXCEED THE SPACE PROVIDED. This project will provide information concerning the relationship of the biochemical parameters of peptide/MHC class I complexes and T cell receptors the generation and preservation of CDS* memory T cells. We will test directly the interplay of affinity and avidity on requirements for costimulation, coreceptor usage and immune responses. These will be investigated by determining the role of affinity in persistence in the memory T cell pool both with and without addition virus exposure. We will also investigate the role of CDS engagement in the persistence of memory. This will directly address the role of CDS mediated signaling in homeostatic proliferation and persistence. Finally we will modify the existing memory pool ifeing toxic MHC-class I tetramers to both alter the memory repertoire and prevent autoimmune disease. These studies will allow us to understand how an individual previous immune history can alter their response to future disease. Further it will allow us to tailor individuals' immune capabilities to reduce the possibility of developing autoimmune disease, while still retaining the ability to fight off new infections. PERFORMANCE SITE ========================================Section End===========================================

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM067143-22
Application #
6889536
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Marino, Pamela
Project Start
1983-02-01
Project End
2007-04-30
Budget Start
2005-05-01
Budget End
2007-04-30
Support Year
22
Fiscal Year
2005
Total Cost
$341,925
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Riddle, David S; Miller, Peter J; Vincent, Benjamin G et al. (2008) Rescue of cytotoxic function in the CD8alpha knockout mouse by removal of MHC class II. Eur J Immunol 38:1511-21
Tian, Shaomin; Maile, Robert; Collins, Edward J et al. (2007) CD8+ T cell activation is governed by TCR-peptide/MHC affinity, not dissociation rate. J Immunol 179:2952-60
Hess, Paul R; Barnes, Carie; Woolard, Matthew D et al. (2007) Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin. Blood 109:3300-7
Maile, Robert; Pop, Shannon M; Tisch, Roland et al. (2006) Low-avidity CD8lo T cells induced by incomplete antigen stimulation in vivo regulate naive higher avidity CD8hi T cell responses to the same antigen. Eur J Immunol 36:397-410
Buchanan, Ian B; Maile, Robert; Frelinger, Jeffrey A et al. (2006) The effect of burn injury on CD8+ and CD4+ T cells in an irradiation model of homeostatic proliferation. J Trauma 61:1062-8
Maile, Robert; Barnes, Carie M; Nielsen, Alma I et al. (2006) Lymphopenia-induced homeostatic proliferation of CD8+ T cells is a mechanism for effective allogeneic skin graft rejection following burn injury. J Immunol 176:6717-26
Maile, Robert; Siler, Catherine A; Kerry, Samantha E et al. (2005) Peripheral ""CD8 tuning"" dynamically modulates the size and responsiveness of an antigen-specific T cell pool in vivo. J Immunol 174:619-27
Kerry, Samantha E; Maile, Robert; Collins, Edward J et al. (2005) Memory CD8 T cells require CD8 coreceptor engagement for calcium mobilization and proliferation, but not cytokine production. Immunology 114:44-52
Lindesmith, Lisa; Moe, Christine; Lependu, Jacques et al. (2005) Cellular and humoral immunity following Snow Mountain virus challenge. J Virol 79:2900-9
Rockx, Barry; Baric, Ralph S; de Grijs, Ingrid et al. (2005) Characterization of the homo- and heterotypic immune responses after natural norovirus infection. J Med Virol 77:439-46

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