Natural killer (NK) cells target virally infected cells and tumor cells through Ly49 receptors that recognize MHC-I molecules. Different inbred mouse strains possess disparate Ly49 receptor haplotypes, in addition to NK cell activity. C5781/6 mice express less Ly49 receptors than 129S1 mice, but have a more robust NK cell population. We intend to determine if the differences in NK cell activity between these inbred mice strains are due to the differences in Ly49 receptor haplotypes. C578116 mice with the Ly49 gene cluster of 129S1 origin were generated in order to compare 129S1 and 86 Ly49 contribution to NK cell function. These B6-Ly49129 congenic mice were confirmed to express the 129 Ly49 receptor pattern by flow cytometry. NK cell activity was assessed by cytotoxicity assays using a panel of NK-resistant and NK-susceptible tumor cell lines, the ability to clear infection with murine cytomegalovirus (MCMV) as well as the ability to reject MHC-I-deficient splenocytes in vivo. Susceptibility to MCMV infection by congenic mice was similar to 129 mice. However, there was a significant increase in rejection of MHC-I-deficient cells by the congenic mice in comparison to both the 86 and 129 mice. In addition, in vitro tumor cell killing by congenic NK cells was comparable to 86. The current results indicate that expression of an increased number of Ly49 receptors promotes better education of NK cells, which in turn leads to higher rejection of MHC deficient target cells.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/28817 |
| Date | January 2010 |
| Creators | Patel, Rajen |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 138 p. |
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