Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by autoantibodies (autoAbs) against desmoglein 3 (Dsg3). Here, we clone anti-Dsg3 antibodies (Abs) from four PV patients and identify pathogenic VH1-46 autoAbs from all four patients. Unexpectedly, VH1-46 autoAbs had relatively few replacement mutations. We reverted antibody somatic mutations to their germline sequences to determine the requirement of mutations for autoreactivity. Three of five VH1-46 germline-reverted Abs maintain Dsg3 binding, compared with zero of five non-VH1-46 germline-reverted Abs. Site-directed mutagenesis of VH1-46 Abs demonstrates that acidic amino-acid residues introduced by somatic mutation or heavy chain VDJ recombination are necessary and sufficient for Dsg3 binding. Our data suggest that VH1-46 autoantibody gene usage is commonly found in PV because VH1-46 Abs require few to no mutations to acquire Dsg3 autoreactivity, which may favour their early selection. Common VH gene usage indicates common humoral immune responses, even among unrelated patients.
Pubmed ID: 24942562
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software that eliminates poorly aligned positions and divergent regions of a DNA or protein alignment so that it becomes more suitable for phylogenetic analysis.
View all literature mentionsIntegrative database of germ-line V genes from the immunoglobulin loci of human and mouse. It presents V gene sequences extracted from the EMBL nucleotide sequence database and Ensembl together with links to the respective source sequences. Based on the properties of the source sequences, V genes are classified into 3 different classes: * Class 1: genomic and rearranged evidence * Class 2: genomic evidence only * Class 3: rearranged evidence only This allows careful sequence quality validation by the user. References to other immunological databases ( KABAT, IMGT/LIGM and VBASE ) are given to provide all public annotation data for each V gene. The VBASE2 database can be accessed either by the Direct Query interface or by the DNAPLOT Query interface. The Sequences given by the user are aligned with DNAPLOT against the VBASE2 database. Direct Query allows to enter sequence IDs and names (Field 1), choose species, locus, V gene family and class (Field 2) or search for 100% sequences (Field 3). At the DNAPLOT Query, the sequences given by the user are aligned with DNAPLOT against the VBASE2 database. The DNAPLOT program offers V gene nucleotide sequence alignment referring to the IMGT V gene unique numbering. The Quick Search can be used either for Direct Query to search for sequence IDs and V gene names or for DNAPLOT Query for up to 5 sequences. The new Fab Analysis allows you to align Fab, scFab, scAb or scFv sequences with DNAPLOT against the VBASE2 database, where both heavy and light chain are analyzed.
View all literature mentions