Epitope Mapping of Pathogenic Autoantigens on Sjögren's Syndrome-Susceptible Human Leukocyte Antigens Using In Silico Techniques.
Shivai GuptaDanmeng LiDavid A OstrovCuong Q NguyenPublished in: Journal of clinical medicine (2022)
Sjögren'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.
Keyphrases
- dendritic cells
- endothelial cells
- high throughput
- case report
- regulatory t cells
- high resolution
- molecular docking
- genome wide association
- pluripotent stem cells
- risk assessment
- oxidative stress
- induced pluripotent stem cells
- gene expression
- peripheral blood
- cell death
- binding protein
- genome wide
- monoclonal antibody
- disease activity
- systemic lupus erythematosus
- cell proliferation
- cell cycle arrest
- mass spectrometry
- molecular dynamics simulations
- signaling pathway
- high density
- single cell
- case control