A synthetic peptide from the third hypervariable region of major histocompatibility complex class II beta chain as a vaccine for treatment of experimental autoimmune encephalomyelitis.

Abstract

Experimental autoimmune encephalomyelitis

Suppression by mAbs against DQB1 peptides ofin vitroproliferation of AChR-specific T cells from myasthenia gravis patients

“…They also exhibited significant bindings to HLA molecules on the cell surface as demonstrated clearly, albeit indirectly, by the inhibition assays using PBLs (Table III). This is in agreement with the previous reports that showed Abs generated against a similar region of mouse MHC class II b-chain recognized the cognate native protein [12,39]. It should be noted that immunogenicity of the peptides in their free forms (i.e.…”

A Conformationally-Constrained MHC Class II I-Ag7-Derived Peptide Protects NOD Mice from the Development of Diabetes

“…Elegant transgenic mouse experiments performed in several laboratories have clearly established that susceptibility to diabetes in NOD mice is strongly associated with the expression of an MHC class II -chain that lacks the usual acidic aspartate residue at position 57, with transgenic introduction of an aspartate at this position protecting animals from development of the disease [18][19][20]. With this insight, and our prior experience with a successful I-A s peptide vaccine utilizing -chain amino acid residues 59-75 to protect SJL mice against EAE [15]; we designed a synthetic peptide vaccine corresponding to -chain amino acid residues 56-77 of the disease-linked MHC class II allele I-A g7 . Vaccination of animals with linear I-A g7 peptide did not modify the incidence of diabetes.…”

“…This approach utilizes immunodominant epitopes from the hypervariable region of the 1-domain of the disease-linked MHC class II molecule to induce an MHC allele-specific immune response capable of subsequently blocking the induction and/or activation of pathology-inducing autoreactive T cells restricted to that particular MHC allele. Preclinical validation of this approach has been obtained using a rodent model of experimental allergic encephalomyelitis (EAE), where geneticallysusceptible SJL/J (I-A s ) mice were protected from disease development when vaccinated with a synthetic peptide derived from the hypervariable region of murine class II MHC I-A s -chain, administered in either a prophylactic or therapeutic mode [15][16].…”

Active immunization with complementary peptide PBM 9-1: preliminary evidence that it modulates experimental allergic encephalomyelitis in PL/J mice and Lewis rats

“…Vaccination with synthetic peptides derived from components of the MHC or TCR offers an attractive approach for the development of specific immunotherapy in autoimmune diseases Araga et al, 1993;Topham et al, 1994). Furthermore, immunization with TCR peptides appears to be well tolerated in humans with multiple sclerosis (MS) (Bourdette et al,Fig.…”

“…Among the numerous immunotherapeutic approaches taken to modulate EAE is that of active immunization or vaccination with synthetic peptides of the major histocompatibility complex (MHC) (Topham et al, 1994) or the T cell receptor (TCR) as well as the administration of antibodies to the MHC (Steinman et al, 1981) or TCR (Zaller et al, 1990). Antibodies reactive with an idiotype (Id) present on encephalitogenic T cells may also reduce the clinical severity of EAE in the Lewis rat (Owhashi and Heber-Katz, 1988) and the PL/J mouse (Zhou and Whitaker, 1993).…”