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Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation.
- Source :
-
JCI insight [JCI Insight] 2021 Jul 08; Vol. 6 (13). Date of Electronic Publication: 2021 Jul 08. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Clone Cells immunology
Epitopes
Genetic Profile
Humans
Immune Reconstitution
Receptors, Antigen, T-Cell immunology
Sequence Analysis, Protein
Transplantation, Homologous adverse effects
Transplantation, Homologous methods
Adaptive Immunity
Complementarity Determining Regions immunology
Graft vs Host Disease immunology
HLA Antigens immunology
Hematopoietic Stem Cell Transplantation adverse effects
Hematopoietic Stem Cell Transplantation methods
Receptors, Antigen, T-Cell, alpha-beta immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 6
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 34236054
- Full Text :
- https://doi.org/10.1172/jci.insight.149080