ID | 113696 |
Title Alternative | 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
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Author |
Khanom, Umme Shahina
University of Tokushima
Ohigashi, Izumi
University of Tokushima
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Fujimori, Sayumi
University of Tokushima
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Kondo, Kenta
National Institutes of Health
Takahama, Yousuke
National Institutes of Health
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Keywords | CD8+ T cells
Peptide
Positive selection
Affinity
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Content Type |
Thesis or Dissertation
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Description | 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.
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Journal Title |
The Journal of Immunology
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ISSN | 00221767
15506606
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NCID | AA12067070
AA00699656
AA12530845
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Publisher | The American Association of Immunologists, Inc.
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Volume | 203
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Issue | 4
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Start Page | 881
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End Page | 887
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Published Date | 2019-06-24
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Remark | 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. |
Rights | Copyright © 2019 by The American Association of Immunologists, Inc.
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3323号
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Diploma Number | 甲医第1425号
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Granted Date | 2019-07-25
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
Institute of Advanced Medical Sciences
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