Please use this identifier to cite or link to this item:
https://doi.org/10.1186/1471-2172-9-30
DC Field | Value | |
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dc.title | Immunological hotspots analyzed by docking simulations: Evidence for a general mechanism in pemphigus vulgaris pathology and transformation | |
dc.contributor.author | Tong, J.C | |
dc.contributor.author | Sinha, A.A | |
dc.date.accessioned | 2020-10-20T04:42:16Z | |
dc.date.available | 2020-10-20T04:42:16Z | |
dc.date.issued | 2008 | |
dc.identifier.citation | Tong, J.C, Sinha, A.A (2008). Immunological hotspots analyzed by docking simulations: Evidence for a general mechanism in pemphigus vulgaris pathology and transformation. BMC Immunology 9 : 30. ScholarBank@NUS Repository. https://doi.org/10.1186/1471-2172-9-30 | |
dc.identifier.issn | 14712172 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/177970 | |
dc.description.abstract | Background: Pemphigus vulgaris (PV) is an acquired autoimmune blistering disorder in which greater than 80% of active patients produce autoantibodies to the desmosomal protein desmogelin 3 (Dsg3). As the disease progresses, 40-50% of patients may also develop reactivity to a second component of the desmosomal complex, desmogelin 1 (Dsg1). T cells are clearly required for the production of autoantibodies in PV. However, few T-cell specificities within Dsg3 or Dsg1 have been reported to date, and the precise role of T-cells in disease pathogenesis and evolution remains poorly understood. In particular, no studies have addressed the immunological mechanisms that underlie the observed clinical heterogeneity in pemphigus. We report here a structure-based technique for the screening of DRB1*0402-specific immunological (T-cell epitope) hotspots in both Dsg3 and Dsg1 glycoproteins. Results: High predictivity was obtained for DRB1*0402 (r2 = 0.90, s = 1.20 kJ/mol, q2 = 0.82, spress = 1.61 kJ/mol) predictive model, compared to experimental data. In silico mapping of the T-cell epitope repertoires in Dsg3 and Dsg1 glycoproteins revealed that the potential immunological hotspots of both target autoantigens are highly conserved, despite limited sequence identity (54% identical, 72% similar). A similar number of well-conserved (18%) high-affinity binders were predicted to exist within both Dsg3 and Dsg1, with analogous distribution of binding registers. Conclusion: This study provides interesting new insights into the possible mechanism for PV disease progression. Our data suggests that the potential T-cell epitope repertoires encoded in Dsg1 and Dsg3 is substantially overlapping, and it may be possible to apply a common, antigen-specific therapeutic strategy with efficacy across distinct clinical phases of disease. © 2008 Tong and Sinha; licensee BioMed Central Ltd. | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | desmoglein 1 | |
dc.subject | desmoglein 3 | |
dc.subject | glycoprotein | |
dc.subject | HLA DR antigen | |
dc.subject | autoantibody | |
dc.subject | desmoglein 1 | |
dc.subject | desmoglein 3 | |
dc.subject | epitope | |
dc.subject | amino acid sequence | |
dc.subject | article | |
dc.subject | binding affinity | |
dc.subject | controlled study | |
dc.subject | disease course | |
dc.subject | epitope mapping | |
dc.subject | immunological technique | |
dc.subject | immunopathology | |
dc.subject | molecular docking | |
dc.subject | molecular model | |
dc.subject | nonhuman | |
dc.subject | pemphigus vulgaris | |
dc.subject | protein binding | |
dc.subject | protein domain | |
dc.subject | protein structure | |
dc.subject | protein targeting | |
dc.subject | screening | |
dc.subject | sequence alignment | |
dc.subject | sequence homology | |
dc.subject | T lymphocyte | |
dc.subject | biological model | |
dc.subject | chemical structure | |
dc.subject | chemistry | |
dc.subject | comparative study | |
dc.subject | computer simulation | |
dc.subject | extracellular space | |
dc.subject | genetics | |
dc.subject | human | |
dc.subject | immunology | |
dc.subject | metabolism | |
dc.subject | molecular genetics | |
dc.subject | pathology | |
dc.subject | pemphigus | |
dc.subject | protein tertiary structure | |
dc.subject | Amino Acid Sequence | |
dc.subject | Autoantibodies | |
dc.subject | Computer Simulation | |
dc.subject | Desmoglein 1 | |
dc.subject | Desmoglein 3 | |
dc.subject | Epitopes, T-Lymphocyte | |
dc.subject | Extracellular Space | |
dc.subject | Humans | |
dc.subject | Models, Immunological | |
dc.subject | Models, Molecular | |
dc.subject | Molecular Sequence Data | |
dc.subject | Pemphigus | |
dc.subject | Protein Structure, Tertiary | |
dc.type | Article | |
dc.contributor.department | BIOCHEMISTRY | |
dc.description.doi | 10.1186/1471-2172-9-30 | |
dc.description.sourcetitle | BMC Immunology | |
dc.description.volume | 9 | |
dc.description.page | 30 | |
Appears in Collections: | Elements Staff Publications |
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