Combining deep mutational scanning to heatmap of HLA class II binding of immunogenic sequences to preserve functionality and mitigate predicted immunogenicity.

ABSTRACT: Removal of CD4 T cell epitopes from therapeutic antibody sequences is expected to mitigate their potential immunogenicity, but its application is complicated by the location of their T cell epitopes, which mainly overlap with complementarity-determining regions. We therefore evaluated the flexibility of antibody sequences to reduce the predicted affinity of corresponding peptides for HLA II molecules and to maintain antibody binding to its target in order to guide antibody engineering for mitigation of predicted immunogenicity. Permissive substitutions to reduce affinity of peptides for HLA II molecules were identified by establishing a heatmap of HLA class II binding using T-cell epitope prediction tools, while permissive substitutions preserving binding to the target were identified by m

SUBMITTER: Sivelle C 

PROVIDER: S-EPMC10416631 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature