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Induction of Anergy by Antibody Blockade of TCR in Myelin Oligodendrocyte Glycoprotein-Specific Cells¹

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322

Previous studies have found that a 95% reduction in TCR expression does not adversely affect response to foreign Ags, indicating that T cells have an excess of TCR for Ag recognition. Because self-reactive T cells may have low affinity for peptide:MHC, we investigated whether myelin-reactive T cells require these excess TCR for optimal response. To test this concept, mAb were used to effectively reduce the TCR of V3.2 and Vβ11 TCR transgenic mice (referred to as 2D2). After masking the TCR with either continuous or prepulsed anti-V3.2 Ab, 2D2 cells were immediately stimulated with myelin oligodendrocyte glycoprotein (MOG)_35–55. These cells have a dramatic Ab dose-dependent reduction in proliferation, with a small reduction in TCR expression leading to a 50% reduction in proliferation in vitro. Additionally, 2D2 cells, treated with anti-V3.2 Ab and peptide for 7 days, were re-stimulated with MOG and continue to have a dose-dependent reduction in proliferation. TCR quantitation identified the same amount of TCR on the Ab/peptide treatment compared with the peptide-only control. These results point out that the combination of reduced TCR and peptide challenge leads to a phenotypic change resulting in T cell anergy. Importantly, adoptive transfer of these anergic T cells upon autoimmune disease induction had a marked reduction in disease severity compared with untreated MOG-specific CD4⁺ T cells, which had significant autoimmune disease manifested by optic neuritis and death. Thus, reduction of TCR expression may provide a potential therapy for self-reactive T cells involved in autoimmune diseases through the induction of anergy.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Multiple Sclerosis Society Grant RG3683.

² Address correspondence and reprint requests to Dr. Brian D. Evavold, Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322. E-mail address: evavold{at}microbio.emory.edu

³ Abbreviations used in this paper: EAE, experimental allergic encephalitis; MOG, myelin oligodendrocyte glycoprotein.

This article has been cited by other articles:

				D. S. Jones, P. Reichardt, M. L. Ford, L. J. Edwards, and B. D. Evavold TCR Antagonism by Peptide Requires High TCR Expression J. Immunol., August 1, 2008; 181(3): 1760 - 1766. [Abstract] [Full Text] [PDF]