アクセス数 : ?
ダウンロード数 : ?
ID 113696
タイトル別表記
胸腺の正の選択におけるTCR親和性は末梢CD8陽性T細胞のTCR応答性を微調整する
IN VIVO PEPTIDES POSITIVELY SELECT AND FINE-TUNE T CELLS
著者
カノン, ウメ シャヒナ 徳島大学大学院医科学教育部(医学専攻)
近藤, 健太 National Institutes of Health
キーワード
CD8+ T cells
Peptide
Positive selection
Affinity
資料タイプ
学位論文
抄録
The affinity for TCR interactions with self-peptide/MHC complexes (pMHC) in the thymus critically affects immature thymocytes that newly express TCRs. Previous fetal thymus organ culture experiments have indicated that difference in the affinity for thymic TCR/pMHC interactions not only determines thymocyte fate between positive and negative selection, but also affects Ag responsiveness of positively selected thymocytes. In the current study, we examined whether TCR/pMHC affinity during positive selection in the thymus would further affect Ag responsiveness of mature T cells in the periphery. To do so, OVA peptide variants were in vivo administered to TAP1-deficient OT-I/TCR-transgenic mice in which T cell development was otherwise arrested at CD4+CD8+ thymocytes because of the lack of self-pMHC presentation in thymic APCs. We found that a group of peptide variants induced the transient generation of OT-I CD8+ T cells in the thymus and the periphery. We also noticed that the affinity threshold for positive and negative selection detected in adult mice in vivo was higher than that measured in fetal thymus organ culture experiments in vitro. Interestingly, we further found that the affinity for positively selecting peptides proportionally affected TCR responsiveness of peripheral naive CD8+ T cells. These results indicate that in vivo administration of a peptide can promote T cell selection in the thymus and the affinity for TCR/pMHC interaction during positive selection fine-tunes Ag responsiveness of peripheral T cells.
掲載誌名
The Journal of Immunology
ISSN
00221767
15506606
cat書誌ID
AA12067070
AA00699656
AA12530845
出版者
The American Association of Immunologists, Inc.
203
4
開始ページ
881
終了ページ
887
発行日
2019-06-24
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Umme Shahina Khanomの学位論文として提出され,学位審査・授与の対象となっている。
Originally published in The Journal of Immunology. Umme Shahina Khanom, Izumi Ohigashi, Sayumi Fujimori, Kenta Kondo, Kensuke Takada, Yousuke Takahama. 2019. TCR Affinity for In Vivo Peptide-Induced Thymic Positive Selection Fine-Tunes TCR Responsiveness of Peripheral CD8+ T Cells. J. Immunol. Vol.203(4) pp881-887.
権利情報
Copyright © 2019 by The American Association of Immunologists, Inc.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3323号
学位記番号
甲医第1425号
学位授与年月日
2019-07-25
学位名
博士(医学)
学位授与機関
徳島大学
部局
先端酵素学研究所