Work

Distorted Immunodominance by Linker Sequences or other Epitopes from a Second Protein Antigen During Antigen-Processing

Year: 2017

Type: article

Abstract: The immune system focuses on and responds to very few representative immunodominant epitopes from pathogenic insults. However, due to the complexity of the antigen processing, understanding the parameters that lead to immunodominance has proved difficult. In an attempt to uncover the determinants of immunodominance among several dominant epitopes, we utilized a cell free antigen processing system and allowed the system to identify the hierarchies among potential determinants. We then tested the results in vivo; in mice and in human. We report here, that immunodominance of known sequences in a given protein can change if two or more proteins are being processed and presented simultaneously. Surprisingly, we find that new spacer/tag sequences commonly added to proteins for purification purposes can distort the capture of the physiological immunodominant epitopes. We warn against adding tags and spacers to candidate vaccines, or recommend cleaving it off before using for vaccination.

Source: Scientific Reports

DOI: 10.1038/srep46418

Authors: AeRyon Kim, Tatiana N. Boronina, Robert N. Cole, Erika Darrah, Scheherazade Sadegh-Nasseri

Institutions: Amgen (United States), Johns Hopkins University, Johns Hopkins Medicine

Language: English

Topic: vaccines and immunoinformatics approaches

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,690

Funders: Jerome L. Greene Foundation, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases