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 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.
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
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