CHARACTERIZATION OF RESTRICTION ELEMENTS UTILIZED BY ANTIGEN-SPECIFIC HELPER T CELL CLONES AND HYBRIDOMAS (MONOCLONAL ANTIBODIES).
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Title
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CHARACTERIZATION OF RESTRICTION ELEMENTS UTILIZED BY ANTIGEN-SPECIFIC HELPER T CELL CLONES AND HYBRIDOMAS (MONOCLONAL ANTIBODIES).
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Identifier
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AAI8501180
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identifier
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8501180
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Creator
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WATERS, STANLEY JOSEPH.
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Contributor
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Constantina A. Bona
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Date
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1984
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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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This study was designed to analyze the restriction elements utilized in the activation and effector function of antigen specific helper T cells. Our first aim was to generate monoclonal T cell populations reactive to keyhole limpet hemocyanin (KLH). Two approaches were employed to clonally expand these antigen specific T cells: (1) non-transformed T cell clones were isolated from antigen primed CB6/F(,1) mice which exhibited proliferation to KLH in the presence of irradiated syngeneic F(,1) spleen cells. (2) T cell hybridomas were also generated by the fusion of KLH reactive lymph node cells from CB6/F(,1) mice with an AKR derived T lymphoma (BWS147). Antigen recognition was measured by the amount of Interleukin-2 (IL-2) secretion by the T cell hybridomas. The panel of monoclonal T cells produced in this manner were characterized in terms of their antigen specificity, surface phenotype, and function. These cells provided a simple, well defined model system to study MHC-restricted T cell interactions. Experiments focused on the genetic restriction of these cells included mapping of restriction elements using recombinant inbred strains of mice, and blocking activation of T cells with monoclonal antibodies specific for polymorphic MHC encoded class II antigens. Functionally active T cell clones proved useful in the study of genetic restriction between T cells and B cells.;Our second aim was to prepare monoclonal antibodies specific for those T cell clones and hybridomas used as immunogens, which could identify idiotype-like determinants on their antigen receptor. One of these antibodies specifically bound to only the immunizing T cell hybridoma FN1-18, but failed to inhibit the antigen specific release of IL-2 by this hybridoma. A second antibody S3a.6-18, raise against a KLH specific T cell line, bound to both hybridoma FN1-18 and a T cell clone A12.11. This antibody prevented KLH recognition by both monoclonal T cell populations. Antibody S3a.6-18 also specifically inhibited the ability of clone A12.11 to cooperate with TNP primed B cell and generate anti-TNP plaques. This data confirms at the level of T cell function, that antibody S3a.6-18 binds to the antigen receptor on clone A12.11. These results also support the hypothesis that the antigen receptor on T cells displays a similar degree of idiotype diversity as immunoglobulin molecules.
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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.
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Program
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Biomedical Sciences
