Identification of self and non-self antigens implicated in autoimmune disease

Abstract

The present invention provides isolated peptides relating to the autoimmune diseases pemphigus vulgaris and multiple sclerosis. The peptides relating to pemphigus vulgaris are self epitopes and those relating to multiple sclerosis are foreign antigens derived from human pathogens which are implicated in the aetiology and remissions of the disease. Pharmaceutical preparations for tolerizing and / or immunizing individuals are provided as well as methods relating thereto. Methods are provided for identifying other self and non-self epitopes involved in human autoimmune disease and similar pharmaceutical preparations and methods of use for these epitopes are also provided.

Description

FIELD OF THE INVENTION [0001] The present invention relates to the field of immunology, and, in particular, to the identification of self and non-self antigens implicated in human autoimmune responses. The invention relates to methods of identifying such self and non-self antigens and provides examples of such antigens relating to multiple sclerosis and pemphigus vulgaris. The invention also relates to the use of such antigens for in vitro assays, animal models, therapeutic agents and vaccines. BACKGROUND OF THE INVENTION [0002] Human autoimmune diseases have a striking genetic association with particular alleles of major histocompatibility complex (“MHC”) class I or class II genes. The field was established by the seminal discovery of HLA-B27 linked susceptibility to ankylosing spondylitis, a chronic inflammatory joint disease (Brewerton et al., 1973; Schlosstein et al., 1973). MHC associated susceptibility has now been documented for a variety of human autoimmune diseases, includi...

AI Technical Summary

Benefits of technology

The present invention provides isolated polypeptides that are associated with the autoimmune disease pemphigus vulgaris and multiple sclerosis, as well as pharmaceutical preparations for tolerizing individuals to these polypeptides. These polypeptides are capable of binding to the HLA-DR protein, which is associated with these autoimmune diseases. The pharmaceutical preparations can be used for immunizing individuals against the pathogens that cause these diseases. The invention also provides methods for using these polypeptides for tolerizing individuals to the self-epitopes associated with pemphigus vulgaris and multiple sclerosis.

Problems solved by technology

No success has been reported using such alignments in identifying epitopes from pathogens that could cross react with presumably pathogenic T cell lines from human patients with autoimmune disease (Oldstone, 1990).

No evidence, however, was provided that these peptides could stimulate clones from diabetic mice (or humans).

Due to the size heterogeneity, however, it has proven more difficult to define MHC class II binding motifs based on sequence alignments.

Even this work, however, could not provide a detailed description of the binding pockets of HLA-DR proteins, the particular residues involved in the formation of these pockets or the structural requirements or antigens for MHC binding.

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