title: Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8(+) T cell receptor alpha repertoire following allogeneic transplantation.
abstract: Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-α repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-α repertoire of CD8(+) T cells and CMV-specific CD8(+) T cells in four patients. Additionally, we performed single-cell TCR-αβ sequencing of CMV-specific CD8(+) T cells. The TCR-α composition of human leucocyte antigen (HLA)-A*0201 CMVpp65- and CMVIE -specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8(+) T cells and half of the total CD8(+) T cell repertoire was dominated by few CMV-reactive clonotypes. Some TCR-α clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8(+) T cells was consistent with chronically activated effector memory T cells. The CD8(+) T cell response to CMV reactivation resulted in an expansion of a few TCR-α clonotypes to dominate the CD8(+) repertoires. These results warrant further larger studies to define the ability of oligoclonally expanded T cell clones to achieve an effective anti-viral T cell response in this setting.
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus.|DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.
authors.forename: C S
authors.initials: CS
authors.lastname: Link
authors.affiliation: DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Eugster
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus.
authors.forename: F
authors.initials: F
authors.lastname: Heidenreich
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus.
authors.forename: E
authors.initials: E
authors.lastname: Rücker-Braun
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus.
authors.forename: M
authors.initials: M
authors.lastname: Schmiedgen
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus.
authors.forename: U
authors.initials: U
authors.lastname: Oelschlägel
authors.affiliation: DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Kühn
authors.affiliation: DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dietz
authors.affiliation: DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Fuchs
authors.affiliation: DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.|BIOTEChnology Center, TU Dresden, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dahl
authors.affiliation: DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.
authors.forename: A M J
authors.initials: AM
authors.lastname: Domingues
authors.affiliation: DKMS Clinical Trials Unit, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Klesse
authors.affiliation: DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.|Institut Für Immunologie, Medizinische Fakultät, TU Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmitz
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus.|DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus.|DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus.|DKMS Clinical Trials Unit, Dresden, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schetelig
authors.affiliation: DFG Research Center for Regenerative Therapies Dresden, Dresden, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Bonifacio
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002999:Clone Cells; D003587:Cytomegalovirus / Q000254:growth & development / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000821:virology; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007156:Immunologic Memory; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D059010:Single-Cell Analysis; D014184:Transplantation, Homologous
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: CMV; T cell receptor alpha; T cell receptor repertoire; allogeneic transplantation; next-generation sequencing