Autoantibodies to T cell receptors in murine models: Specificity and gene usage

Persistent Link:
http://hdl.handle.net/10150/282143
Title:
Autoantibodies to T cell receptors in murine models: Specificity and gene usage
Author:
Dehghanpisheh, Keivan, 1969-
Issue Date:
1996
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The goal of this dissertation was to develop a murine model in which to study autoantibodies that arise naturally and are targeted towards T cell receptor beta chains. The method utilized was the production of monoclonal B cell hybridomas secreting these autoantibodies. The impetus for this work was the observation that the sera of mice, rabbits and humans carry antibodies directed towards peptide defined epitopes of the T cell receptor (TCR) beta chain, along with the findings that the levels of these autoantibodies are modulated with autoimmune disease. The first study involved motheaten mice, which develop spontaneous fatal autoimmune disease as a result of a recessive point mutation. Here we report on the novel gene usage of one monoclonal derived from motheaten mice that exhibits unusual binding activities. We also derived monoclonals from mice infected with the LP-BM5 retrovirus mixture. This infection results in an autoimmune state and is considered by us to be a good model of autoimmunity induced by an infectious agent. The retrovirally induced monoclonals bind TCR vp complementarity determining region 1 (CDR1) peptides, recombinant single chain TCR molecules and T cells. One monoclonal, ATM-1 binds a restricted panel of CDR1 peptides while ATM-2 exhibits a broad range of specificities for the CDR1 peptides. The Vbeta genes encoding these two autoantibodies represent distinct Vbeta subfamilies with amino acid replacements in the CDR2 being associated with the narrow binding specificity. Both monoclonal autoantibodies costimulate superantigen induced proliferation of unfractionated mouse splenocytes. The etiologic agents of anti-TCR autoantibody elaboration and consequences of overproduction are discussed in the context of infectious autoimmunity murine models and autoimmunity in general.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Molecular.; Biology, Cell.; Chemistry, Biochemistry.; Health Sciences, Immunology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Microbiology and Immunology
Degree Grantor:
University of Arizona
Advisor:
Marchalonis, John J.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleAutoantibodies to T cell receptors in murine models: Specificity and gene usageen_US
dc.creatorDehghanpisheh, Keivan, 1969-en_US
dc.contributor.authorDehghanpisheh, Keivan, 1969-en_US
dc.date.issued1996en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe goal of this dissertation was to develop a murine model in which to study autoantibodies that arise naturally and are targeted towards T cell receptor beta chains. The method utilized was the production of monoclonal B cell hybridomas secreting these autoantibodies. The impetus for this work was the observation that the sera of mice, rabbits and humans carry antibodies directed towards peptide defined epitopes of the T cell receptor (TCR) beta chain, along with the findings that the levels of these autoantibodies are modulated with autoimmune disease. The first study involved motheaten mice, which develop spontaneous fatal autoimmune disease as a result of a recessive point mutation. Here we report on the novel gene usage of one monoclonal derived from motheaten mice that exhibits unusual binding activities. We also derived monoclonals from mice infected with the LP-BM5 retrovirus mixture. This infection results in an autoimmune state and is considered by us to be a good model of autoimmunity induced by an infectious agent. The retrovirally induced monoclonals bind TCR vp complementarity determining region 1 (CDR1) peptides, recombinant single chain TCR molecules and T cells. One monoclonal, ATM-1 binds a restricted panel of CDR1 peptides while ATM-2 exhibits a broad range of specificities for the CDR1 peptides. The Vbeta genes encoding these two autoantibodies represent distinct Vbeta subfamilies with amino acid replacements in the CDR2 being associated with the narrow binding specificity. Both monoclonal autoantibodies costimulate superantigen induced proliferation of unfractionated mouse splenocytes. The etiologic agents of anti-TCR autoantibody elaboration and consequences of overproduction are discussed in the context of infectious autoimmunity murine models and autoimmunity in general.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Molecular.en_US
dc.subjectBiology, Cell.en_US
dc.subjectChemistry, Biochemistry.en_US
dc.subjectHealth Sciences, Immunology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMicrobiology and Immunologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMarchalonis, John J.en_US
dc.identifier.proquest9713356en_US
dc.identifier.bibrecord.b34338755en_US
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