抄録
Foreign protein Ags are incorporated into APCs and then degraded by endosomal proteases. The peptides are then mounted on MHC II molecules on the surfaces of APCs. The T cell-triggering response and, therefore, the immune response, were suggested to be governed by the degree of conformational stability of the foreign protein Ags. However, there is little evidence that a protein's conformational stability is an immunologically dominant factor. In this study, we show that a protein has a threshold of conformational stability to prevent the immunogenicity of foreign proteins. Inverse and linear correlations were found between the amount of IgG production against lysozymes and the free-energy change for the unfolding of lysozymes, based on the correlation between the free-energy changes of the protein unfolding and the amount of IgG production against lysozymes with different stabilities in mice using hen egg white lysozyme derivatives and mutant mouse lysozymes, in which the sequence between 107 and 116 is replaced with that of hen egg white lysozyme, which can produce autoantibodies in mice. Interestingly, the thresholds of free-energy changes for both lysozymes to prevent their immunogenicity were almost identical (21-23 kcal/mol). To confirm the results, we also showed that the cross-linking of Phl p 7, in which intact Phl p 7 has stability greater than ∼20 kcal/mol under physiological conditions, induced minimal IgG production in mice, whereas intact Phl p 7 was antigenic. From the above results, we suggest that protein conformational stability was an immunologically dominant factor.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 4199-4205 |
| ページ数 | 7 |
| ジャーナル | Journal of Immunology |
| 巻 | 185 |
| 発行部数 | 7 |
| DOI | |
| 出版物ステータス | 出版済み - 10 1 2010 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
これを引用
A protein's conformational stability is an immunologically dominant factor : Evidence that free-energy barriers for protein unfolding limit the immunogenicity of foreign proteins. / Ohkuri, Takatoshi; Nagatomo, Satoko; Oda, Kenji; So, Takanori; Imoto, Taiji; Ueda, Tadashi.
：: Journal of Immunology, 巻 185, 番号 7, 01.10.2010, p. 4199-4205.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - A protein's conformational stability is an immunologically dominant factor
T2 - Evidence that free-energy barriers for protein unfolding limit the immunogenicity of foreign proteins
AU - Ohkuri, Takatoshi
AU - Nagatomo, Satoko
AU - Oda, Kenji
AU - So, Takanori
AU - Imoto, Taiji
AU - Ueda, Tadashi
PY - 2010/10/1
Y1 - 2010/10/1
N2 - Foreign protein Ags are incorporated into APCs and then degraded by endosomal proteases. The peptides are then mounted on MHC II molecules on the surfaces of APCs. The T cell-triggering response and, therefore, the immune response, were suggested to be governed by the degree of conformational stability of the foreign protein Ags. However, there is little evidence that a protein's conformational stability is an immunologically dominant factor. In this study, we show that a protein has a threshold of conformational stability to prevent the immunogenicity of foreign proteins. Inverse and linear correlations were found between the amount of IgG production against lysozymes and the free-energy change for the unfolding of lysozymes, based on the correlation between the free-energy changes of the protein unfolding and the amount of IgG production against lysozymes with different stabilities in mice using hen egg white lysozyme derivatives and mutant mouse lysozymes, in which the sequence between 107 and 116 is replaced with that of hen egg white lysozyme, which can produce autoantibodies in mice. Interestingly, the thresholds of free-energy changes for both lysozymes to prevent their immunogenicity were almost identical (21-23 kcal/mol). To confirm the results, we also showed that the cross-linking of Phl p 7, in which intact Phl p 7 has stability greater than ∼20 kcal/mol under physiological conditions, induced minimal IgG production in mice, whereas intact Phl p 7 was antigenic. From the above results, we suggest that protein conformational stability was an immunologically dominant factor.
AB - Foreign protein Ags are incorporated into APCs and then degraded by endosomal proteases. The peptides are then mounted on MHC II molecules on the surfaces of APCs. The T cell-triggering response and, therefore, the immune response, were suggested to be governed by the degree of conformational stability of the foreign protein Ags. However, there is little evidence that a protein's conformational stability is an immunologically dominant factor. In this study, we show that a protein has a threshold of conformational stability to prevent the immunogenicity of foreign proteins. Inverse and linear correlations were found between the amount of IgG production against lysozymes and the free-energy change for the unfolding of lysozymes, based on the correlation between the free-energy changes of the protein unfolding and the amount of IgG production against lysozymes with different stabilities in mice using hen egg white lysozyme derivatives and mutant mouse lysozymes, in which the sequence between 107 and 116 is replaced with that of hen egg white lysozyme, which can produce autoantibodies in mice. Interestingly, the thresholds of free-energy changes for both lysozymes to prevent their immunogenicity were almost identical (21-23 kcal/mol). To confirm the results, we also showed that the cross-linking of Phl p 7, in which intact Phl p 7 has stability greater than ∼20 kcal/mol under physiological conditions, induced minimal IgG production in mice, whereas intact Phl p 7 was antigenic. From the above results, we suggest that protein conformational stability was an immunologically dominant factor.
UR - http://www.scopus.com/inward/record.url?scp=77958130059&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77958130059&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0902249
DO - 10.4049/jimmunol.0902249
M3 - Article
C2 - 20817878
AN - SCOPUS:77958130059
VL - 185
SP - 4199
EP - 4205
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -