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...

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Bibliographic Details
Published in:JCI insight 2021-07, Vol.6 (13)
Main Authors: 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
Format: Article
Language:English
Subjects:
Adaptive Immunity
Clone Cells - immunology
Complementarity Determining Regions - immunology
Epitopes
Genetic Profile
Graft vs Host Disease - immunology
Hematology
Hematopoietic Stem Cell Transplantation - adverse effects
Hematopoietic Stem Cell Transplantation - methods
HLA Antigens - immunology
Humans
Immune Reconstitution
Immunology
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell, alpha-beta - immunology
Sequence Analysis, Protein
Transplantation, Homologous - adverse effects
Transplantation, Homologous - methods
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Summary: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.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.149080