Modulating adaptive immune responses to peptide self-assemblies.

Area of Science:

• Biomaterials Science
• Immunology
• Nanotechnology

Background:

• Self-assembling peptides are promising for biomedical uses like tissue engineering and drug delivery.
• Their immunogenicity varies greatly, posing challenges for therapeutic development.
• Current strategies to control peptide immunogenicity are underdeveloped.

Purpose of the Study:

• To investigate the molecular and immunological factors driving the immunogenicity of the self-assembling peptide OVA-Q11.
• To explore methods for modulating peptide immunogenicity for desired biomedical outcomes.

Main Methods:

• Adoptive transfer experiments in mice.
• T cell knockout models.
• Amino acid region deletion and residue mutation in peptides.
• Analysis of self-assembly and fibrillization.

Main Results:

• OVA-Q11 elicits strong, T cell-dependent antibody responses lasting at least one year.
• Deleting T cell-recognized regions diminished immunogenicity.
• Mutating self-assembly domains reduced immunogenicity by preventing fibrillization.
• OVA-KFE8 nanofibers, but not the peptide alone, induced strong antibody responses, indicating sequence-independent adjuvant effects.

Conclusions:

• Peptide immunogenicity is T cell-dependent and influenced by self-assembly properties.
• Strategies targeting T cell epitopes and self-assembly can control immune responses.
• Findings enable rational design of peptide biomaterials for applications requiring controlled immunogenicity.