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Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation
TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR archi...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410023/ https://www.ncbi.nlm.nih.gov/pubmed/34236054 http://dx.doi.org/10.1172/jci.insight.149080 |
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author | Pagliuca, Simona Gurnari, Carmelo Hong, Sanghee Zhao, Ran Kongkiatkamon, Sunisa Terkawi, Laila Zawit, Misam Guan, Yihong Awada, Hassan Kishtagari, Ashwin Kerr, Cassandra M. LaFramboise, Thomas Patel, Bhumika J. Jha, Babal K. Carraway, Hetty E. Visconte, Valeria Majhail, Navneet S. Hamilton, Betty K. Maciejewski, Jaroslaw P. |
author_facet | Pagliuca, Simona Gurnari, Carmelo Hong, Sanghee Zhao, Ran Kongkiatkamon, Sunisa Terkawi, Laila Zawit, Misam Guan, Yihong Awada, Hassan Kishtagari, Ashwin Kerr, Cassandra M. LaFramboise, Thomas Patel, Bhumika J. Jha, Babal K. Carraway, Hetty E. Visconte, Valeria Majhail, Navneet S. Hamilton, Betty K. Maciejewski, Jaroslaw P. |
author_sort | Pagliuca, Simona |
collection | PubMed |
description | TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes. Donor and pretransplant TCR diversity as well as divergence of class I human leukocyte antigen genotypes were major predictors of recipient TCR repertoire recovery. Complementary determining region 3–based specificity spectrum analysis indicated a predominant expansion of pathogen- and tumor-associated clonotypes in the late post–allo-HCT phase, while autoreactive clones were more expanded in the case of graft-versus-host disease occurrence. These findings shed light on post–allo-HCT adaptive immune reconstitution processes and possibly help in tracking alloreactive responses. |
format | Online Article Text |
id | pubmed-8410023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-84100232021-09-07 Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation Pagliuca, Simona Gurnari, Carmelo Hong, Sanghee Zhao, Ran Kongkiatkamon, Sunisa Terkawi, Laila Zawit, Misam Guan, Yihong Awada, Hassan Kishtagari, Ashwin Kerr, Cassandra M. LaFramboise, Thomas Patel, Bhumika J. Jha, Babal K. Carraway, Hetty E. Visconte, Valeria Majhail, Navneet S. Hamilton, Betty K. Maciejewski, Jaroslaw P. JCI Insight Research Article TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes. Donor and pretransplant TCR diversity as well as divergence of class I human leukocyte antigen genotypes were major predictors of recipient TCR repertoire recovery. Complementary determining region 3–based specificity spectrum analysis indicated a predominant expansion of pathogen- and tumor-associated clonotypes in the late post–allo-HCT phase, while autoreactive clones were more expanded in the case of graft-versus-host disease occurrence. These findings shed light on post–allo-HCT adaptive immune reconstitution processes and possibly help in tracking alloreactive responses. American Society for Clinical Investigation 2021-07-08 /pmc/articles/PMC8410023/ /pubmed/34236054 http://dx.doi.org/10.1172/jci.insight.149080 Text en © 2021 Pagliuca et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Pagliuca, Simona Gurnari, Carmelo Hong, Sanghee Zhao, Ran Kongkiatkamon, Sunisa Terkawi, Laila Zawit, Misam Guan, Yihong Awada, Hassan Kishtagari, Ashwin Kerr, Cassandra M. LaFramboise, Thomas Patel, Bhumika J. Jha, Babal K. Carraway, Hetty E. Visconte, Valeria Majhail, Navneet S. Hamilton, Betty K. Maciejewski, Jaroslaw P. Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation |
title | Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation |
title_full | Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation |
title_fullStr | Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation |
title_full_unstemmed | Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation |
title_short | Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation |
title_sort | clinical and basic implications of dynamic t cell receptor clonotyping in hematopoietic cell transplantation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410023/ https://www.ncbi.nlm.nih.gov/pubmed/34236054 http://dx.doi.org/10.1172/jci.insight.149080 |
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