Next-generation version of recombinant human interferon-beta: A molecular dynamic simulation study

Abstract

The ability of recombinant human interferon beta-1b (IFNβ-1b) to elicit the production of anti-IFNβ-1b antibodies becomes a significant issue for interferon therapy in patients. Mitigating the immunogenicity issues requires understanding the stimulating factors in observed immune responses. Among multiple factors, epitopes might be the main reason for the observed immunogenicity of this drug. In this study, we investigate the ability of epitopes in IFNβ-1b to bind to the MHC class II receptors. We applied point mutations to reduce the binding affinity of the existing epitopes of IFNβ-1b to MHC class II molecules. Several bioinformatics methods were applied to compare the binding affinity of both native and mutated epitopes to the MHC class II receptors. We identified three residues, Tyrosine 3, Tyrosine 132, and Glycine 162, that if altered to Leucine, Leucine, and Glutamate, respectively, leads to a decline in the binding affinity of IFNβ-1 b's epitope to the MHC class II receptors.This suggests that we can decline the binding affinity of therapeutic IFNβ-1b in silico by introducing those point mutations.