The objective of this project continues to be the study of the structure, function and expression of lymphocyte cell surface glycoproteins. The long-term goal is to contribute to an understanding of immune function and hematopoietic differentiation. Molecular biologic techniques in combination with immunological analysis using monoclonal antibodies and protein biochemistry will be used to extend ongoing studies of three cell membrane proteins, T200, the IL-2 receptor and Pgp-1.
The specific aims are to determine the molecular basis for the different forms of T200 expressed on specific subpopulations of lymphocytes and to develop new methods to study the function. The genomic structure of murine T200 will be determined and cDNAs from murine and human T and B cells will be isolated and sequenced. Anti-sense T200 retroviral constructs will be used to attempt to suppress T200 expression in CTL lines. The structural requirements for human IL-2 receptor-ligand interaction will be investigated. Proteolytic cleavage experiments demonstrate that the external region of the IL-2 receptor is composed of two domains and that the N-terminal domain forms an integral part of the IL-2 binding site. The N-terminal domain and other regions of the IL-2 receptor will be expressed in bacterial and eukaryotic expression systems to obtain sufficient protein to prepare monoclonal antibodies and for structure-function analysis. Finally, collaborative studies are proposed to obtain cDNA clones of Pgp-1 glycoprotein and to determine its primary structure.
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