Autoimmune Responses to Soluble Aggregates of Amyloidogenic Proteins Involved in Neurodegenerative Diseases: Overlapping Aggregation Prone and Autoimmunogenic regions

摘要: Why do patients suffering from neurodegenerative diseases generate autoantibodies that selectively bind soluble aggregates of amyloidogenic proteins? Presently, molecular basis interactions between the and human immune system is unknown. By analyzing sequences experimentally validated T-cell autoimmune epitopes, aggregating peptides, proteins randomly generated here we report overlapping regions likely drive aggregation as well against aggregates. Sequence features, make short peptides susceptible to aggregation, increase their incidence in epitopes by 4–6 times. Many are predicted be significantly prone (aggregation propensities ≥10%) ones containing enriched hydrophobicity 10–20%. Aggregate morphologies also influence Human Leukocyte Antigen (HLA) - types recognized epitopes. Most (88%) contain amyloid fibril forming HLA-DR, while majority (63%) those amorphous β-aggregating HLA-DQ. More than two-thirds (70%) simultaneously auto-immunogenic. Such help clear generating selective them. This can harnessed for early diagnosis proteinopathies drug/vaccine design