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