Binding and functional properties of natural anti-T cell receptor antibodies in patients with rheumatoid arthritis

Persistent Link:
http://hdl.handle.net/10150/289736
Title:
Binding and functional properties of natural anti-T cell receptor antibodies in patients with rheumatoid arthritis
Author:
Robey, Ian Forrest
Issue Date:
2001
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:
Natural autoantibodies specific for the T cell receptor (TCR) are present in all human sera. Differences in titer, epitope specificity, and isotype depend on physiological condition, viral infections, or the presence of autoimmune diseases. Individuals with rheumatoid arthritis (RA) make significantly higher titers of IgM isotype autoantibodies demonstrating major reactivity for the CDR1 region of the Vβ TCR. To establish a more intimate understanding of the role of these antibodies in the immune system we generated B cell hetero-hybridomas secreting monoclonal IgM autoantibodies from the synovial tissue and peripheral blood of RA patients. We report molecular and partial functional characterization of seven IgM anti-TCR monoclonal antibodies (mAbs). These autoantibodies were selected on a recombinant TCR and peptide epitopes and bind JURKAT human T cell lines and a subset of CD3⁺ human peripheral blood mononuclear cells (PBMCs) in flow cytometry experiments. The V regions of these antibodies were generally identical to germline sequences in both the heavy and the light chains and the heavy-chain CDR3 segments did not correspond to known antibody sequence. Three of these anti-TCR mAbs, OR2, ORS, and Syn 2H-11, demonstrated an antigen specific binding property defined as epitope recognition promiscuity. The molecules did not act as rheumatoid factors. These same mAbs bound to subsets of murine T cells and TCR peptide epitopes. The autoantibodies did not induce apoptosis in vitro, but prevented IL-2 production by antigen-specific T cells. These findings describe a unique group of immunoregulatory antibodies and represent a foundation for further investigations and their eventual use as therapeutic agents in human disease.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
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.titleBinding and functional properties of natural anti-T cell receptor antibodies in patients with rheumatoid arthritisen_US
dc.creatorRobey, Ian Forresten_US
dc.contributor.authorRobey, Ian Forresten_US
dc.date.issued2001en_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.abstractNatural autoantibodies specific for the T cell receptor (TCR) are present in all human sera. Differences in titer, epitope specificity, and isotype depend on physiological condition, viral infections, or the presence of autoimmune diseases. Individuals with rheumatoid arthritis (RA) make significantly higher titers of IgM isotype autoantibodies demonstrating major reactivity for the CDR1 region of the Vβ TCR. To establish a more intimate understanding of the role of these antibodies in the immune system we generated B cell hetero-hybridomas secreting monoclonal IgM autoantibodies from the synovial tissue and peripheral blood of RA patients. We report molecular and partial functional characterization of seven IgM anti-TCR monoclonal antibodies (mAbs). These autoantibodies were selected on a recombinant TCR and peptide epitopes and bind JURKAT human T cell lines and a subset of CD3⁺ human peripheral blood mononuclear cells (PBMCs) in flow cytometry experiments. The V regions of these antibodies were generally identical to germline sequences in both the heavy and the light chains and the heavy-chain CDR3 segments did not correspond to known antibody sequence. Three of these anti-TCR mAbs, OR2, ORS, and Syn 2H-11, demonstrated an antigen specific binding property defined as epitope recognition promiscuity. The molecules did not act as rheumatoid factors. These same mAbs bound to subsets of murine T cells and TCR peptide epitopes. The autoantibodies did not induce apoptosis in vitro, but prevented IL-2 production by antigen-specific T cells. These findings describe a unique group of immunoregulatory antibodies and represent a foundation for further investigations and their eventual use as therapeutic agents in human disease.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)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.proquest3031383en_US
dc.identifier.bibrecord.b42286463en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.