application): The studies proposed in this project are based on ongoing research on the molecular and cellular basis of host defense reactions against influenza virus. These investigators have already produced a large panel of hybridomas producing monoclonal antibodies specific for the hemagglutinin (GA) or PRS influenza virus and have transgenic mice expressing the Valpha and Vbeta genes of a T cell hybridoma that recognize an immunodominant peptide of HA corresponding to amino acid residues 110-120 of HA recognized by CD4 T cells in association to amino acid residues 110-120 of HA recognized by CD4 T cells in association with I-Ed molecules.
The specific aims of the project are: (1) To study the effect of aging on somatic mutation in protective antibodies against influenza virus. The investigators will generate a large panel of HA-specific hybridomas from K-knockout mice of various ages in order to compare the extent of somatic mutations in the genes. The rate of spontaneous mutations will be studied in transgenic line provided by Dr. R. Pollack. (2) To determine whether aging influences the persistence and function of T cell clone specific for an immunodominant epitope of influenza virus HA. To achieve this specific for an immunodominant epitope of influenza virus HA. To achieve this aim they will take advantage of transgenic mice which express Va and Vb transgene from a T cell hybridoma that recognizes HA110-120 peptide in association with I-Ed- molecules. In the transgenic mice the Valpha and Vbeta transgenes are expressed in CD4 and CD8 T cells. The ability of CD4 T cells to develop a proliferative response upon in vitro incubation with various carriers expressing HA110-120 peptide and the ability of CD8 T cells to lyse target cells coated HA 110-120 peptide will be determined. Since the evolution of a T cell clone may be affected by microbial exposure during aging they propose to study whether the exposure to influenza virus during aging affects the T cell clone expressing the CRT transgene.
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