Common Neurodegeneration-Associated Proteins Are Physiologically Expressed by Human B Lymphocytes and Are Interconnected via the Inflammation/Autophagy-Related Proteins TRAF6 and SQSTM1.

摘要: There is circumstantial evidence that, under neurodegenerative conditions, peptides deriving from aggregated or misfolded specific proteins elicit adaptive immune responses. On another hand, several genes involved in familial forms of diseases exert key innate functions. However, whether not such observations are causally linked remains unknown. To start addressing this issue, we followed a systems biology strategy based on the mining large proteomics and immunopeptidomics databases. First, retrieved expression patterns common neurodegeneration-associated two professional antigen-presenting cells, namely B lymphocytes dendritic cells. Surprisingly, found that physiological numerous abundantly expressed by human lymphocytes. A survey proteome allowed us to map unique protein-protein interaction network linking their first shell interactors Interestingly, connectivity analysis identified major hubs both relate with inflammation autophagy, TRAF6 (TNF Receptor Associated Factor 6) SQSTM1 (Sequestosome-1). Moreover, mapped comprised additional hub autoimmunity: HSPA8 (Heat Shock Protein Family Member 8 also known as HSC70) HSP90AA1 90 Alpha Class 1). Based these results, then explored Immune Epitope Database "IEDB-AR" actually share were previously reported provide endogenous MHC class II-binding Of note, amyloid beta A4 protein, sequestosome-1 profilin-1 bind multiple allele-specific II molecules. In contrast, microtubule-associated protein tau, presenilin 2 serine/threonine-protein kinase TBK1 exclusively molecules encoded HLA-DRB1 1501 allele, recently-identified susceptibility gene for late onset Alzheimer's disease. Finally, observed whole list specifically enriched proteins. Overall, our work indicates immunization against might be process which shaped, at least part,