Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation.
Fiche publication
Date publication
juillet 2021
Journal
JCI insight
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PAGLIUCA Simona
Tous les auteurs :
Pagliuca S, Gurnari C, Hong S, Zhao R, Kongkiatkamon S, Terkawi L, Zawit M, Guan Y, Awada H, Kishtagari A, Kerr CM, LaFramboise T, Patel BJ, Jha BK, Carraway HE, Visconte V, Majhail NS, Hamilton BK, Maciejewski JP
Lien Pubmed
Résumé
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.
Mots clés
Adaptive immunity, Hematology, Immunology, T cell receptor
Référence
JCI Insight. 2021 07 8;6(13):