Binding and functional properties of natural anti-T cell receptor antibodies in patients with rheumatoid arthritis
AuthorRobey, Ian Forrest
KeywordsHealth Sciences, Immunology.
AdvisorMarchalonis, John J.
MetadataShow full item record
PublisherThe University of Arizona.
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.
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.
Degree ProgramGraduate College
Microbiology and Immunology