TCED™ and iTope™ – A powerful tool for in silico immunogenicity assessment
The combination of iTope™, MHC Class II binding prediction, and TCED™, T cell epitope database, provides a more accurate prediction of T cell epitopes than other in silico technologies that rely solely on MHC class II binding analysis. TCED™ and iTope™ are ideal for rapid screening of large numbers of protein sequences to identify potential leads with reduced risk of immunogenicity for further development. They can also aid in the design of deimmunised proteins and antibodies.
iTope™ – Peptide/MHC Class II Binding
iTope™ is a proprietary in silico molecular modelling technology which models the binding between amino acid side chains of a peptide and specific binding pockets within the binding grooves of 34 human MHC class II alleles. The contribution of individual amino acids to peptide binding can be determined for each allele and this provides information on the precise location of the core 9mer sequences that interact with the MHC class II binding groove. iTope™ provides a useful first step in evaluating the immunogenic potential of antibodies and proteins but, in common with other in silico binding technologies, iTope™ significantly over-predicts the presence of CD4+ T cell epitopes, and is thus best used prior to immunogenicity screening using EpiScreen™. For immunogenic amino acid sequences already identified using T cell epitope mapping, iTope™ determines the core 9mer sequences that can be used to design non-antigenic sequence variants in which T cell epitopes are mutated to disrupt MHC Class II binding.
TCED™ – T Cell Epitope Database™
Data from EpiScreen™ T cell epitope mapping studies conducted over a decade have enabled us to develop a database of CD4+ T cell epitopes. Sequences from antibodies and proteins that are candidates for development as therapeutic agents can be analysed for homology to these known T cell epitopes, enabling the rapid and accurate in silico identification of their potential to produce an immunogenic response. Furthermore, homology to peptides in the database that do not contain T cell epitopes provides a valuable source of sequences that are used as a base for the generation of Composite Human Antibody™ or Composite Protein™, our humanized antibody and deimmunised protein technologies.
TCED™ and iTope™ combined for better prediction of immunogenicity
TCED™ and iTope™ can be used in combination to provide a more accurate evaluation of potential immunogenicity. Sequences within a test protein that are identified as having a high probability of containing T cell epitopes in silico can, if required, then be tested using EpiScreen™.
The combined TCED™/iTope™ technology is typically used for rapid analysis of multiple sequences (eg, from therapeutic antibody candidates) in order to identify a strong lead sequence with a reduced risk of immunogenicity.
Below: Analysis of a protein sequence using iTope™ & TCED™. Peptides spanning the test sequence were tested as 9mer peptides in one amino acid increments. The position of p1 anchor residues comprises the first residue of an MHC class II ligand core 9mer. Regions containing potentially immunogenic peptides are indicated in left hand columns where red indicates promiscuous high affinity MHC class II binding peptides and yellow indicates promiscuous moderate affinity MHC class II binding peptides. In the “TCED™” column, regions representing closely homologous peptides from the T cell epitope database are shown in green.
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