Engineering N-glycosylation mutations in IL-12 enhances sustained cytotoxic T lymphocyte responses for DNA immunization

Nature Biotechnology
Sang J HaYoung C Sung

Abstract

Interleukin-12 (IL-12), consisting of p40 and p35 subunits, produces both p70 heterodimer and free p40. p70 is essential for the induction of T-helper 1 (Th1) and cytotoxic T-cell (CTL) immunity, whereas p40 inhibits p70-mediated function. Here, we found that mutations introduced into N-glycosylation sites (N220 of murine p40 and N222 of human p40) reduced secretion of p40 but not p70. Co-immunization of N220 mutant mIL-12 gene with hepatitis C virus (HCV) E2 DNA significantly enhanced long-term E2-specific CD8+ T-cell response and protection against tumor challenge compared with that of wild type. Our results indicate that the ratio of p70 to p40 is important for generating sustained long-term cell-mediated immunity. Thus, the mutant IL-12 could be utilized for the development of DNA vaccines as an adjuvant for the generation of long-term memory T-cell responses.

References

Apr 1, 1992·Archives of Biochemistry and Biophysics·F J PodlaskiA S Stern
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·A S SternR Chizzonite
Oct 31, 1996·Annals of the New York Academy of Sciences·M K GatelyD H Presky
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·H N LodeR A Reisfeld
Oct 2, 1998·Advances in Immunology·G Trinchieri
Apr 26, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·G CarraG Trinchieri
Apr 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·W C KieperS C Jameson
May 9, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·D F ToughJ Sprent

❮ Previous
Next ❯

Citations

Jul 25, 2003·Archives of Pharmacal Research·Byong-Moon KimWon-Bae Kim
Nov 30, 2005·Transgenic Research·Abel Gutiérrez-OrtegaMiguel Angel Gómez-Lim
Apr 17, 2003·Trends in Immunology·Frank BrombacherGottfried Alber
Jul 3, 2008·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Jianyun LiuCarole L Cramer
Dec 30, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Giuliana MedranoCarole L Cramer
Oct 7, 2004·Biological & Pharmaceutical Bulletin·Hiroko ShibataYasuo Tsutsumi
Mar 3, 2004·Biotechnology and Bioengineering·Abel Gutiérrez-OrtegaMiguel Angel Gómez-Lim
Oct 21, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Byung Woo HwangSei Kwang Hahn
Feb 2, 2006·Journal of Theoretical Biology·David J Klinke
Sep 2, 2004·British Medical Bulletin·Peter KarayiannisHoward C Thomas
Aug 8, 2014·Advanced Healthcare Materials·Junseok YeomSei Kwang Hahn
Dec 1, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jin-Won YounYoung Chul Sung
Dec 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sang-Jun HaYoung-Chul Sung
May 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Doo-Jin KimYoung-Chul Sung
Feb 16, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Antonie ZwiersGerd Bouma
Feb 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jun ChangYoung-Chul Sung
Feb 19, 2003·Biochemical and Biophysical Research Communications·Zev WilliamsPaul M Wassarman

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.