IN VIVO PEPTIDES POSITIVELY SELECT AND FINE-TUNE T CELLS
KHANOM, UMME SHAHINA University of Tokushima
Ohigashi, Izumi University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Fujimori, Sayumi University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kondo, Kenta National Institutes of Health
Takada, Kensuke University of Tokushima KAKEN Search Researchers
Takahama, Yousuke National Institutes of Health Tokushima University Educator and Researcher Directory KAKEN Search Researchers
CD8+ T cells
Thesis or Dissertation
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.
The Journal of Immunology
The American Association of Immunologists, Inc.
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.
Copyright © 2019 by The American Association of Immunologists, Inc.
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Doctor of Medical Science
Institute of Advanced Medical Sciences