Human monoclonal natural autoantibodies against the T-cell receptor inhibit interleukin-2 production in murine T cells.
Natural autoantibodies (NAAbs) specific for the T-cell receptor (TCR) are present in all human sera, but individuals with rheumatoid arthritis (RA) generally produce higher titres of immunoglobulin M (IgM) isotype autoantibodies (AAbs) against Vbeta TCR epitopes. To investigate possible correlations between the specificity of such AAbs and their role in immunomodulation, we generated seven B-cell hetero-hybridomas, secreting monoclonal IgM NAAbs, from the synovial tissue and peripheral blood of patients with RA. Here we report three anti-TCR monoclonal autoantibodies (mAAbs)--OR2, OR5 and Syn 2H-11--with the ability to bind subsets of murine T cells, including the ovalbumin-specific DO-11.10 clone. These antibodies did not induce apoptosis in vitro, but prevented interleukin-2 (IL-2) production by antigen-specific T cells. These findings suggest an immunomodulatory function for NAAbs to TCR V-region epitopes and serve as the foundation for testing human anti-TCR mAAbs in animal models with the eventual goal of using them as therapeutic agents in human disease.
Robey
Ian F
IF
Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Schluter
Samuel F
SF
Akporiaye
Emmanuel
E
Yocum
David E
DE
Marchalonis
John J
JJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas; D007376:Interleukin-2 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell