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Li Zuo, Constance M Cullen, Monica L DeLay, Sherry Thornton, Linda K Myers, Edward F Rosloniec, Gregory P Boivin, Raphael Hirsch, A Single-Chain Class II MHC-IgG3 Fusion Protein Inhibits Autoimmune Arthritis by Induction of Antigen-Specific Hyporesponsiveness, The Journal of Immunology, Volume 168, Issue 5, March 2002, Pages 2554–2559, https://doi.org/10.4049/jimmunol.168.5.2554
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Abstract
T cells play a central role in many autoimmune diseases. A method to specifically target the function of autoreactive T cell clones would avoid the global immunosuppression associated with current therapies. To develop a molecule capable of inhibiting autoreactive T cell responses in vivo, single-chain peptide-I-A-IgG3 fusion proteins were constructed and expressed in both mammalian and insect cells. The fusion proteins were designed with an IgG3 Fc moiety to make them divalent, allowing TCR cross-linking, while lacking FcR binding and costimulation. The fusion proteins stimulated T cell hybridomas in vitro in a peptide-specific, MHC-restricted manner but failed to do so in soluble form. In vivo administration of an I-Aq fusion protein, containing an immunodominant collagen II peptide, significantly delayed the onset and reduced the severity of collagen-induced arthritis in DBA/1 mice by induction of Ag-specific hyporesponsiveness. Such fusion proteins may be useful to study novel therapeutic approaches for T cell-mediated autoimmune diseases.
