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

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

Abstract

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