During the present grant period we propose to carry out studies in 3 areas relating to proteins expressed on the surface of human T cells: 1) Human T Cell Receptors. The expression of both TCR alpha beta and TCR gamma delta will be studied using cloned genes encoding the various chains of these receptors. Some aspects of the cell biology and functions of these receptors will be examined. The ultimate goal is to engineer these genes in order to produce soluble TCR alpha beta and TCR gamma delta, to produce these soluble receptors in large amounts and to crystallize them. 2) Pulmonary sarcoidosis. A primary goal is to culture and clone the T cells from bronchoalveolar lavage of patients with this disease with a view to characterizing them phenotypically and functionally. In particular we wish to examine the question of whether or not these T cells are oligoclonal and utilize one or a small number of T cell receptor alpha and beta gene V, D and J segments. 3) The 4F2 protein. This heterodimeric protein is the first activation antigen detected on the surface of human T cells. We wish to complete the cloning of the genes of this protein and use them to study the mechanism of activation of their transcription and their role in cell proliferation.
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