CD4+ T-Cell Epitope Prediction by Combined Analysis of Antigen Conformational Flexibility and Peptide-MHCII Binding Affinity.

ABSTRACT: Antigen processing in the class II MHC pathway depends on conventional proteolytic enzymes, potentially acting on antigens in native-like conformational states. CD4+ epitope dominance arises from a competition among antigen folding, proteolysis, and MHCII binding. Protease-sensitive sites, linear antibody epitopes, and CD4+ T-cell epitopes were mapped in plague vaccine candidate F1-V to evaluate the various contributions to CD4+ epitope dominance. Using X-ray crystal structures, antigen processing likelihood (APL) predicts CD4+ epitopes with significant accuracy for F1-V without considering peptide-MHCII binding affinity. We also show that APL achieves excellent performance over two benchmark antigen sets. The profiles of conformational flexibility derived from the X-ray crystal structures

SUBMITTER: Charles T 

PROVIDER: S-EPMC9352311 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature