IL-2/neuroantigen fusion proteins as antigen-specific tolerogens in experimental autoimmune encephalomyelitis (EAE): correlation of T cell-mediated antigen presentation and tolerance induction.

The purpose of this study was to assess whether the Ag-targeting activity of cytokine/neuroantigen (NAg) fusion proteins may be associated with mechanisms of tolerance induction. To assess this question, we expressed fusion proteins comprised of a N-terminal cytokine domain and a C-terminal NAg domain. The cytokine domain comprised either rat IL-2 or IL-4, and the NAg domain comprised the dominant encephalitogenic determinant of the guinea pig myelin basic protein.

Cytokine-neuroantigen fusion proteins: new tools for modulation of myelin basic protein (MBP)-specific T cell responses in experimental autoimmune encephalomyelitis.

Fusion proteins incorporating anti-inflammatory cytokines and immunodominant self antigen as separate domains of a single protein may hold promise for development of antigen-specific tolerogenic vaccines. Proteins incorporating rat sequences of IL-1RA, IL-2, IL-4, IL-10, or IL-13 were expressed as fusion proteins containing the major encephalitogenic region of myelin basic protein (MBP). These fusion proteins were expressed via baculovirus (bv) expression systems and were shown to have cytokine-dependent and antigen-specific biological activity.

MHC class II biosynthesis by activated rat CD4+ T cells: development of repression in vitro and modulation by APC-derived signals.

This study focused on synthesis of MHC class II glycoproteins (MHCII) by rat CD4(+) T-helper cells. During activation in Con A and IL-2, purified rat splenic CD4(+) T cells expressed abundant surface MHCII together with transcripts for I-A alpha/beta, invariant chain, and the type III and type IV MHC class II transactivator (CIITA). Activated thymic CD8(+)CD4(-) and CD8(+)CD4(+) T cells exhibited essentially the same phenotype.