PMID- 35330015 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220330 IS - 2077-0383 (Print) IS - 2077-0383 (Electronic) IS - 2077-0383 (Linking) VI - 11 IP - 6 DP - 2022 Mar 18 TI - Epitope Mapping of Pathogenic Autoantigens on Sjogren's Syndrome-Susceptible Human Leukocyte Antigens Using In Silico Techniques. LID - 10.3390/jcm11061690 [doi] LID - 1690 AB - 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. FAU - Gupta, Shivai AU - Gupta S AD - Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA. FAU - Li, Danmeng AU - Li D AUID- ORCID: 0000-0002-6905-554X AD - Department of Pathology, Immunology & Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA. FAU - Ostrov, David A AU - Ostrov DA AUID- ORCID: 0000-0002-4696-875X AD - Department of Pathology, Immunology & Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA. FAU - Nguyen, Cuong Q AU - Nguyen CQ AUID- ORCID: 0000-0001-5633-4075 AD - Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA. AD - Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA. AD - Center of Orphaned Autoimmune Diseases, University of Florida, Gainesville, FL 32611, USA. LA - eng GR - R01 DE028544/DE/NIDCR NIH HHS/United States PT - Journal Article DEP - 20220318 PL - Switzerland TA - J Clin Med JT - Journal of clinical medicine JID - 101606588 PMC - PMC8953074 OTO - NOTNLM OT - T cells OT - autoantigens OT - human leukocyte antigen (HLA) OT - major histocompatibility complex (MHC) COIS- The authors declare no conflict of interest. EDAT- 2022/03/26 06:00 MHDA- 2022/03/26 06:01 PMCR- 2022/03/18 CRDT- 2022/03/25 01:12 PHST- 2022/02/02 00:00 [received] PHST- 2022/03/03 00:00 [revised] PHST- 2022/03/08 00:00 [accepted] PHST- 2022/03/25 01:12 [entrez] PHST- 2022/03/26 06:00 [pubmed] PHST- 2022/03/26 06:01 [medline] PHST- 2022/03/18 00:00 [pmc-release] AID - jcm11061690 [pii] AID - jcm-11-01690 [pii] AID - 10.3390/jcm11061690 [doi] PST - epublish SO - J Clin Med. 2022 Mar 18;11(6):1690. doi: 10.3390/jcm11061690.