This research investigates human lymphocyte cell surface molecules relevant to immune function. The methodology is based on the production of murine monoclonal antibodies recognizing distinct differentiation antigens. With these reagents, it is possible to identify both immature T cells and mature functionally distinct T-cell subsets. Selected antibodies can also be used as probes to study the function and potential receptor role of specific T-cell surface molecules. By generating panels of antibodies capable of recognizing different epitopes on functionally significant molecules, it will be possible to explore the relationship between structure and function. Selected antibodies will also be used for the isolation and purification of specific molecules for biochemical characterization and amino acid sequencing. Experiments are directed towards identifying differentiation markers for suppressor cell subsets as well as for surface molecules that may be uniquely related to suppressor cell function. Clinically, these studies are relevant to the further understanding of the pathogenesis of immune deficiency disorders such as those occurring in the acquired immunodeficiency syndrome (AIDS), certain patients with malignancy, hemophiliacs, and in patients following bone marrow transplantation. Immune reconstitution and complications related to immunodeficiency constitute major issues in clinical marrow transplantation. We will address these questions by evaluating the kinetics of lymphoid reconstitution and by characterizing the functional capacity of cells appearing during the post-transplant period, especially immature lymphoid cells. The identification of immature lymphocytes, or precursor T cells, will provide the opportunity to study the potential effects of lymphokines and thymic hormones and on thymic epithelial cell monolayers as means for induction of differentiation and maturation. This could have general relevance to further understanding and treatment of multiple immune deficiency disorders. (CS)
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