| NSF Org: |
MCB Division of Molecular and Cellular Biosciences |
| Recipient: |
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| Initial Amendment Date: | March 29, 2002 |
| Latest Amendment Date: | September 7, 2004 |
| Award Number: | 0136536 |
| Award Instrument: | Continuing Grant |
| Program Manager: |
Eve Ida Barak
MCB Division of Molecular and Cellular Biosciences BIO Directorate for Biological Sciences |
| Start Date: | May 1, 2002 |
| End Date: | April 30, 2006 (Estimated) |
| Total Intended Award Amount: | $525,321.00 |
| Total Awarded Amount to Date: | $532,821.00 |
| Funds Obligated to Date: |
FY 2003 = $176,114.00 FY 2004 = $185,433.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
910 GENESEE ST ROCHESTER NY US 14611-3847 (585)275-4031 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
910 GENESEE ST ROCHESTER NY US 14611-3847 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): |
INSTRUMENTAT & INSTRUMENT DEVP, Cellular Dynamics and Function, SIGNAL TRANSDCTN/CELL REGULATN |
| Primary Program Source: |
app-0103 app-0104 |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
CD8 cytotoxic T-lymphocytes (CTL) recognize and kill targets that express antigenic peptides in the context of major histocompatibility complex (MHC) class I molecules. As such, CTL are crucially involved in the generation of adaptive immunity against viruses and tumors. Natural killer (NK) cells play an active role in innate immunity by detecting and killing virally-infected or tumor cells that have down-regulated their surface MHC class I molecules thereby escaping surveillance by the adaptive immune system. Growing evidence suggests that some immune responses are mediated by CTL expressing NK-associated molecules (CD8/NK T-cells). The biology and physiological significance of the complexity and heterogeneity of NK-associated molecules and their expression by different effectors (e.g. CTL) is unclear. Since it is now well established in several species, including frogs, that certain heat shock proteins (e.g. gp96 or hsp70) elicit both adaptive CD8 T-cell mediated responses against the antigenic peptides they chaperone, and innate immune responses, it will be of significance to explore, for the first time, the extent to which this putative ancestral system of hsp-generated immunity may involve CTL that express NK-associated molecules. In addition, an unequivocal characterization of NK/T-cells in an amphibian that occupies a pivotal position in the evolution of vertebrates would support the hypothesis that CD8 NK/T-cells represent an important evolutionary step that bridges the innate and adaptive immune systems. This finding would also attest of the importance of this cell type in immunity of mammals. Finally, a better knowledge of cell-mediated cytotoxicity in Xenopus may have crucial implication with respect to understanding putative defects in the immune defense systems used against those viral pathogens that are causing world-wide declines of amphibian populations. The overall goal of this project is to take advantage of our Xenopus model to assess, from an evolutionary perspective, the role of CD8 NK/T cells, both in vitro and in vivo, in innate and adaptive immune responses to tumor, viral, and minor histocompatibility antigens as well as to explore the idea that T-cells co-expressing CD8 and NK markers (CD8 NK/T-cells) are phylogenetically early mediators of cellular immunity.
Natural killer and cytotoxic T-lymphocytes are two important types of immune cells involved in defense against virus infections and tumor. Recent studies suggest the existence of a novel cell type with intermediate characteristics. The goal of the research program is to use the frog Xenopus rather than mice as a model system to better understand the role of this new type of immune cell in immune defense against cancer and virus infections from an evolutionary perspective.
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