Visualising the Immune Repertoire
Author(s): Svetlana Mollova, Ida Retter, Werner Müller
Affiliations: Helmholtz Centre for Infection Research, Technical University of Braunschweig, University of Manchester
Keywords: 'keyword_1' 'add_keyword_2' 'add_keyword_3' 'add_keyword_4'
Antibodies play a central role in the adaptive immune defense of all vertebrates. Thereby, the specific recognition of antigen structures by antibody molecules determines the success of the immune response. For this reason, the repertoire of antigen binding sites within the immune system of an individuum, but also, within a population, has been a mean focus of immunological research within the last 3 decades. The first tool to analyse the DNA sequence of the antigen binding site of an antibody was DNAPLOT. Associated with the Vbase database, the DNAPLOT search page was the first of its kind which allowed the analysis of the modular composition of of these binding sites, the immunoglobulin gene rearrangements. The focus of this site was to identify and mark the genetics elements that are used for these rearrangements. In the meantime, several similar tools are available, including the current DNAPLOT version associated with the VBASE2 database.
We have now introduced a major extension to the functionality of DNAPLOT. The new features allow the systematic analysis and visualization of the expressed immune repertoire of an organism. Thus, DNAPLOT is now able to demonstrate the dynamics of the expressed repertoire, e.g., during the time course of the antibody response against a certain pathogen. Looking at antibody structures, it is well known that mainly the so-called complementary determining regions (CDRs) contain the information of the interface between a given antibody and its antigen. The adjacent regions, the so-called framework regions (FRs), build the antibody structure and provide a frame to expose the 3 CDR regions of each variable domain of an antibody. The new extended DNAPLOT version loads a list of variable domain DNA sequences, extracts the CDR regions and presents them as a color-coded string of amino acids. In this way, the essential information on the docking sites of a given antibody population is easily visible, and critical amino acids can be viewed at a glance. The new DNAPLOT extension is not only applicable for the analysis of naturally occuring immune repertoires but also for the analysis of artificial antibody populations isolated from phage display libraries.
The program DNAPLOT displays characteristics and dynamics of a given natural or artificial immunoglobulin repertoire. By removing redundant information, essential information about the antigen binding sites is condensed and visualized.