A single-chain class II MHC-IgG3 fusion protein inhibits autoimmune arthritis by induction of antigen-specific hyporesponsiveness

Li Zuo, Constance M. Cullen, Monica L. DeLay, Sherry Thornton, Linda Myers, Edward F. Rosloniec, Gregory P. Boivin, Raphael Hirsch

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2554-2559
Number of pages6
JournalJournal of Immunology
Volume168
Issue number5
DOIs
StatePublished - Mar 1 2002
Externally publishedYes

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Arthritis
Immunoglobulin G
T-Lymphocytes
Antigens
Proteins
Peptides
Autoimmune Diseases
Inbred DBA Mouse
Experimental Arthritis
Hybridomas
Immunosuppression
Insects
Collagen
Clone Cells
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

A single-chain class II MHC-IgG3 fusion protein inhibits autoimmune arthritis by induction of antigen-specific hyporesponsiveness. / Zuo, Li; Cullen, Constance M.; DeLay, Monica L.; Thornton, Sherry; Myers, Linda; Rosloniec, Edward F.; Boivin, Gregory P.; Hirsch, Raphael.

In: Journal of Immunology, Vol. 168, No. 5, 01.03.2002, p. 2554-2559.

Research output: Contribution to journalArticle

Zuo, Li ; Cullen, Constance M. ; DeLay, Monica L. ; Thornton, Sherry ; Myers, Linda ; Rosloniec, Edward F. ; Boivin, Gregory P. ; Hirsch, Raphael. / A single-chain class II MHC-IgG3 fusion protein inhibits autoimmune arthritis by induction of antigen-specific hyporesponsiveness. In: Journal of Immunology. 2002 ; Vol. 168, No. 5. pp. 2554-2559.
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