Please use this identifier to cite or link to this item: https://doi.org/10.1186/1471-2172-9-30
Title: Immunological hotspots analyzed by docking simulations: Evidence for a general mechanism in pemphigus vulgaris pathology and transformation
Authors: Tong, J.C 
Sinha, A.A
Keywords: desmoglein 1
desmoglein 3
glycoprotein
HLA DR antigen
autoantibody
desmoglein 1
desmoglein 3
epitope
amino acid sequence
article
binding affinity
controlled study
disease course
epitope mapping
immunological technique
immunopathology
molecular docking
molecular model
nonhuman
pemphigus vulgaris
protein binding
protein domain
protein structure
protein targeting
screening
sequence alignment
sequence homology
T lymphocyte
biological model
chemical structure
chemistry
comparative study
computer simulation
extracellular space
genetics
human
immunology
metabolism
molecular genetics
pathology
pemphigus
protein tertiary structure
Amino Acid Sequence
Autoantibodies
Computer Simulation
Desmoglein 1
Desmoglein 3
Epitopes, T-Lymphocyte
Extracellular Space
Humans
Models, Immunological
Models, Molecular
Molecular Sequence Data
Pemphigus
Protein Structure, Tertiary
Issue Date: 2008
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
Rights: Attribution 4.0 International
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.
Source Title: BMC Immunology
URI: https://scholarbank.nus.edu.sg/handle/10635/177970
ISSN: 14712172
DOI: 10.1186/1471-2172-9-30
Rights: Attribution 4.0 International
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