Shape of the art: TCR-repertoire after allogeneic hematopoietic cell transplantation

Abstract

The human adaptive immune repertoire is characterized by specificity and diversity to provide immunity against past and future tasks. Such tasks are mainly infections but also malignant transformations of cells. With its multiple lines of defense, the human immune system contains both, rapid reaction forces and the potential to capture, disassemble and analyze strange structures in order to teach the adaptive immune system and mount a specific immune response. Prevention and mitigation of autoimmunity is of equal importance. In the context of allogeneic hematopoietic cell transplantation (HCT) specific challenges exist with the transfer of cells from the adapted donor immune system to the immunosuppressed recipient. Those challenges are immunogenetic disparity between donor and host, reconstitution of immunity early after HCT by expansion of mature immune effector cells, and impaired thymic function, if the recipient is an adult (as it is the case in most HCTs). The possibility to characterize the adaptive immune repertoire by massively parallel sequencing of T-cell receptor gene rearrangements allows for a much more detailed characterization of the T-cell repertoire. In addition, high-dimensional characterization of immune effector cells based on their immunophenotype and single cell RNA sequencing allow for much deeper insights in adaptive immune responses. We here review, existing - still incomplete - information on immune reconstitution after allogeneic HCT. Building on the technological advances much deeper insights into immune recovery after HCT and adaptive immune responses and can be expected in the coming years.

Keywords: Allogeneic hematopoietic cell transplantation; Cytomegalovirus (CMV); T-cell receptor repertoire; T-cell reconstitution; Thymus.