Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation

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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.
Funding Information
  • NIH Office of the Director (R35 HL135795,R01HL123904,R01 380HL118281,R01 HL128425,R01 HL132071)
  • Società Italiana di Ematologia Sperimentale (Lo Coco Scholarship)
  • Fondation ARC pour la Recherche sur le Cancer (Prix de mobilité)

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