The purpose of this project is to continue studies on the function of the Ly-6A/E alloantigens in the immune system at both the cellular and molecular levels in four major areas of investigation. First, the possibility that Ly-6A/E marks a specific lineage of T cells will be examined by experiments which characterize the phenotype of mature T cells which develop from Ly-6A/E+ and Ly-6A/E- precursor cells and in studies which examine the function of Ly-6A/E+ and Ly-6A/E- CD4 and CD8 mature T cells. A second group of studies will explore the molecular basis by which an anti-Ly-6A/E mAb blocks IL-2 production of T cell hybridomas and normal T cells stimulated through the CD3/TcR complex. In part, these studies will focus on changes in expression of individual CD3 components or in patterns of phosphorylation of CD3 subunits for cells activated through Ly-6A/E. The possibility that the Ly-6 pathway may regulate IL-2 at transcriptional or posttranscriptional levels will also be determined. This group of experiments will also test the basis for the apparent IL-2 independent proliferation of alloantigen-stimulated T cells when cultured in the presence of an anti-Ly-6A/E mAb. Third, the modulation of B cell function will be further characterized by examining whether immunoglobulin isotype expression is altered after stimulation of B cells through Ly-6 molecules. Binding studies to Ly-6A/E will be performed with cells transfected with Ly-6A/E cDNA or purified Ly-6A/E protein in attempts to identify the physiological ligand for Ly-6A/E. These studies should extend our knowledge of the role of Ly-6 molecules in immune responses and may be relevant to cancer and autoimmunity since Ly-6 proteins are abnormally expressed or regulated in these diseases.
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