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

Sang J. Ha; Jun Chang; Man K. Song; You S. Suh; Hyun T. Jin; Chu H. Lee; Gyu H. Nam; Gildon Choi; Kwan Y. Choi; Sung H. Lee; Won B. Kim; Young C. Sung

doi:10.1038/nbt0402-381

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

Sang J. Ha
, Jun Chang
, Man K. Song
, You S. Suh
, Hyun T. Jin
, Chu H. Lee
, Gyu H. Nam
, Gildon Choi
, Kwan Y. Choi
, Sung H. Lee
, Won B. Kim
, Young C. Sung

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

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 mlL-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 lL-12 could be utilized for the development of DNA vaccines as an adjuvant for the generation of long-term memory T-cell responses.

Original language	English
Pages (from-to)	381-386
Number of pages	6
Journal	Nature Biotechnology
Volume	20
Issue number	4
DOIs	https://doi.org/10.1038/nbt0402-381
State	Published - Apr 2002

Bibliographical note

Funding Information:
Acknowledgments The authors acknowledge Sang-Chun Lee and Su-Il Park for devoted animal care. We are grateful to Hye-Ryun Kim and Se-Hwan Yang for faithful reading and comments. This work was supported by National Research Laboratory grant from Korea Institute of Science and Technology Evaluation and Planning (2000-N-NL-01-C-202) and grants from POSCO (2000Y013), Superior Research Center supported by Korea Science and Engineering Foundation, and ProGen Co. Ltd.

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10.1038/nbt0402-381

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@article{a0b87ba86fd74bd49b13b7c0e822a33d,

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

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 mlL-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 lL-12 could be utilized for the development of DNA vaccines as an adjuvant for the generation of long-term memory T-cell responses.",

author = "Ha, \{Sang J.\} and Jun Chang and Song, \{Man K.\} and Suh, \{You S.\} and Jin, \{Hyun T.\} and Lee, \{Chu H.\} and Nam, \{Gyu H.\} and Gildon Choi and Choi, \{Kwan Y.\} and Lee, \{Sung H.\} and Kim, \{Won B.\} and Sung, \{Young C.\}",

note = "Funding Information: Acknowledgments The authors acknowledge Sang-Chun Lee and Su-Il Park for devoted animal care. We are grateful to Hye-Ryun Kim and Se-Hwan Yang for faithful reading and comments. This work was supported by National Research Laboratory grant from Korea Institute of Science and Technology Evaluation and Planning (2000-N-NL-01-C-202) and grants from POSCO (2000Y013), Superior Research Center supported by Korea Science and Engineering Foundation, and ProGen Co. Ltd.",

year = "2002",

month = apr,

doi = "10.1038/nbt0402-381",

language = "English",

volume = "20",

pages = "381--386",

journal = "Nature Biotechnology",

issn = "1087-0156",

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T1 - Engineering N-glycosylation mutations in IL-12 enhances sustained cytotoxic T lymphocyte responses for DNA immunization

AU - Ha, Sang J.

AU - Chang, Jun

AU - Song, Man K.

AU - Suh, You S.

AU - Jin, Hyun T.

AU - Lee, Chu H.

AU - Nam, Gyu H.

AU - Choi, Gildon

AU - Choi, Kwan Y.

AU - Lee, Sung H.

AU - Kim, Won B.

AU - Sung, Young C.

N1 - Funding Information: Acknowledgments The authors acknowledge Sang-Chun Lee and Su-Il Park for devoted animal care. We are grateful to Hye-Ryun Kim and Se-Hwan Yang for faithful reading and comments. This work was supported by National Research Laboratory grant from Korea Institute of Science and Technology Evaluation and Planning (2000-N-NL-01-C-202) and grants from POSCO (2000Y013), Superior Research Center supported by Korea Science and Engineering Foundation, and ProGen Co. Ltd.

PY - 2002/4

Y1 - 2002/4

N2 - 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 mlL-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 lL-12 could be utilized for the development of DNA vaccines as an adjuvant for the generation of long-term memory T-cell responses.

AB - 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 mlL-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 lL-12 could be utilized for the development of DNA vaccines as an adjuvant for the generation of long-term memory T-cell responses.

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DO - 10.1038/nbt0402-381

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EP - 386

JO - Nature Biotechnology

JF - Nature Biotechnology

IS - 4

ER -

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

Abstract

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