Epitope Mapping of Pathogenic Autoantigens on Sjogren's Syndrome-Susceptible Human Leukocyte Antigens Using In Silico Techniques

Sjogren's syndrome (SjS) is characterized by lymphocytic infiltration and the dysfunction of the salivary and lacrimal glands. The autoimmune response is driven by the effector T cells and their cytokines. The activation of the effector helper T cells is mediated by autoantigen presentation by human leukocyte antigen (HLA) class II molecules of antigen-presenting cells. Studies using familial aggregation, animal models, and genome-wide association demonstrate a significant genetic correlation between specific risk HLAs and SjS. One of the key HLA alleles is HLA-DRB1*0301; it is one of the most influential associations with primary SjS, having the highest odds ratio and occurrence across different ethnic groups. The specific autoantigens attributed to SjS remain elusive, especially the specific antigenic epitopes presented by HLA-DRB1*0301. This study applied a high throughput in silico mapping technique to identify antigenic epitopes of known SjS autoantigens presented by high-risk HLAs. Furthermore, we identified specific binding HLA-DRB1*0301 epitopes using structural modeling tools such as Immune Epitope Database and Analysis Resource IEDB, AutoDock Vina, and COOT. By deciphering the critical epitopes of autoantigens presented by HLA-DRB1*0301, we gain a better understanding of the origin of the antigens, determine the T cell receptor function, learn the mechanism of disease progression, and develop therapeutic applications.

Automated summary

Sjogren's syndrome is characterized by lymphocytic infiltration and dysfunction of salivary and lacrimal glands. Studies have shown a significant genetic correlation between specific risk HLAs and SjS, with HLA-DRB1*0301 being particularly influential. The specific autoantigens attributed to SjS and the epitopes presented by HLA-DRB1*0301 remain elusive, requiring further research.