Bioinformatics-Based Predictions of Peptide Binding to Disease-Associated HLA Proteins Suggest Explanation for Shared Autoimmunity

摘要: Aim: This study was designed to examine the immunogenetic basis for shared autoimmunity, resulting in autoantigen presentation that leads production of two or more disease-specific autoantibodies. Methods: A bioinformatics approach based on peptide binding predictions disease-associated HLA determinants has been developed and tested here using 11 disease associations between autoimmune systemic mucocutaneous blistering disorders. Various HLAs associated with antigens within a given “disease model” (set class II protein sequences known be specific disease) were ranked against antigenic proteins, first proteins they are associate then implicated second model. In every case compared different same HLA. Subsequently, disease-related autoantigens have their affinity each protein. Results: For single haplotype, several binders generated from related variable score. most cases, score corresponding interactions autoantigen-derived epitope one similar lower than Notably, there no compelling promiscuity molecules, spite promiscuous nature binding. Conclusions: The data suggest that, susceptible individuals, autoimmunity might initiated by types HLA/peptide interaction; an its second, disease.