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

Ae Ryon Kim, Tatiana N. Boronina, Robert N. Cole, Erika Darrah, Scheherazade Sadegh-Nasseri

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number46418
JournalScientific Reports
Volume7
DOIs
StatePublished - Apr 19 2017

Fingerprint

Antigen Presentation
Epitopes
Antigens
Proteins
Immunodominant Epitopes
Immune System
Vaccination
Vaccines

ASJC Scopus subject areas

  • General

Cite this

@article{f34ba14f61564fea90a42f7ed93d879b,
title = "Distorted Immunodominance by Linker Sequences or other Epitopes from a Second Protein Antigen during Antigen-Processing",
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.",
author = "Kim, {Ae Ryon} and Boronina, {Tatiana N.} and Cole, {Robert N.} and Erika Darrah and Scheherazade Sadegh-Nasseri",
year = "2017",
month = "4",
doi = "10.1038/srep46418",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Distorted Immunodominance by Linker Sequences or other Epitopes from a Second Protein Antigen during Antigen-Processing

AU - Kim,Ae Ryon

AU - Boronina,Tatiana N.

AU - Cole,Robert N.

AU - Darrah,Erika

AU - Sadegh-Nasseri,Scheherazade

PY - 2017/4/19

Y1 - 2017/4/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85017596260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017596260&partnerID=8YFLogxK

U2 - 10.1038/srep46418

DO - 10.1038/srep46418

M3 - Article

VL - 7

JO - Scientific Reports

T2 - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 46418

ER -