The objective of this proposal is to characterize the receptors for the Fc fragment of IgG present on human cell effectors in natural self-defense mechanisms. The two major classes of Fc receptors, Mo-FcR for monomeric immunoglobulins, present on monocytes and interferon-treated myeloid cells, and PMN-FcR for complexed IgG present on mature myeloid and NK/K cells, will be characterized biochemically. Their molecular structure, enzyme sensitivity, intra- and extra-cellular distribution on peripheral blood cell subsets, normal bone marrow, leukemic cells, and myelomonocytic cell lines will be defined. The control of the expression of FcR, their function in the different cell types, and the possible heterogeneity within them will be analyzed. The experimental approach includes the production of additional monoclonal antibodies directed against distinct epitopes of PMN-FcR and against Mo-FcR. The antibodies will be used to precipitate the Fc-binding proteins, to study their Ig-binding characteristics, to define their differential expression on the different cell types, to detect lymphocyte subpopulations bearing FcR, and to define the stage of myelomonocytic differentiation at which the receptors are expressed. The role of the different FcR types in FcR-dependent functions will be investigated. Chromosomal mapping of the gene(s) encoding the different FcR will be attempted using the monoclonal antibodies to determine the phenotype and select clones of human-mouse somatic cell hybrids. (CS)
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