The objective of this project is to use monoclonal antibodies to identify and characterize specific cell surface molecules of murine hematopoietic cells and to use these antibodies as probes to study hematopoietic differentiation. The Pgp-1 glycoprotein is present on a variety of hematopoietic cell lineages but is absent on most cells of the thymus. Only 5 to 20% of the cells in the thymus are Pgp-1?+?. We are studying the nature of these Pgp-1?+? thymus cells, using assays for thymic stem cells, and are studying the ontogeny of Pgp-1?+? cells in the thymus during fetal development. Intrathymic stem cells that can transiently repopulate the thymus of an irradiated animal are Pgp-1?+?. Furthermore, nearly all thymocytes in the 13 to 14 day fetal mouse are Pgp-1?+?. These results indicate that certain Pgp-1?+? cells have the properties expected of intrathymic progenitor cells. Antibody against the transferrin receptor has been considered as a possible immunotherapeutic reagent. We have isolated a number of monoclonal antibodies against the murine transferrin receptor, some of which block cell growth. Mutants of lymphoma cell lines that escape the growth inhibitory action of the antibodies have been isolated. We are studying the genetic mechanisms by which these mutant cells arise and are using the mutants and the antibodies to study aspects of transferrin receptor function. (CS)
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