Role of differential class II antigen expression in allostimulation by human monocyte hybridomas.
Item
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Title
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Role of differential class II antigen expression in allostimulation by human monocyte hybridomas.
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Identifier
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AAI9009781
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identifier
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9009781
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Creator
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Shaked, Abraham.
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Contributor
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Adviser: Lloyd F. Mayer
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Date
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1989
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Language
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English
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Publisher
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City University of New York.
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Subject
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Health Sciences, Immunology
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Abstract
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A series of human monocyte hybridomas were generated by the fusion of {dollar}\gamma{dollar} -IFN activated peripheral blood monocytes with an HGPRT deficient promonocytic cell line, U937. Fusion efficiency related to the use of {dollar}\gamma{dollar} -IFN as the monocyte activator and ranged between 1-3%. These fusion products were determined to be true hybridomas by their acquisition of donor HLA class I gene products. In addition, these cells displayed morphologic characteristics distinct from the U937 parent line, hyperploidy, as well as functional characteristics of normal mature monocytes (IL-1 and CSF secretion, Fc mediated rosetting and phagocytosis of immune complexes). One unusual aspect of these hybrids was the differential expression of class II antigens, HLA-DR, DP and DQ. Only one hybrid clone, 16.1, expressed HLA-DR whereas others, 13 and 15, expressed DP and DQ but no DR and the U937 parent line was class II Ag negative. We utilized this unusual phenotype to address the role of individual class II Ags in the stimulation of an allogeneic mixed lymphocyte reaction. All three class II Ags were stimulatory in MLR as determined by the ability of clones 16, 13 and 15 but not U937 to stimulate allogeneic T cells. Further evidence for this finding was obtained by the ability of antibodies against distinct class II Ags to inhibit MLRs in a manner which correlated to the pattern of class II Ag expression on the hybrids. In addition, {dollar}\gamma{dollar} -IFN appeared to differentially regulate DP and DQ expression on the hybrids, downregulating expression on clones 16, 13 and 15 and upregulating expression on U937 and clone 8. The expression of DP and DQ directly correlated with the ability of these cells to stimulate a primary allogeneic MLR. Furthermore, when we analyzed the phenotype and function of responding T cells in the individual MLR cultures, it appeared that there was a preference for CD8+ T cells in MLRs where the stimulator was DR{dollar}-{dollar} but DP, DQ+. Taken together, these data suggest that distinct class II Ags may play an important role in the regulation of T cell responses and that specific T cell subpopulations may be D sub-region restricted.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
