title: Persistence of EBV antigen-specific CD8 T cell clonotypes during homeostatic immune reconstitution in cancer patients.
abstract: Persistent viruses are kept in check by specific lymphocytes. The clonal T cell receptor (TCR) repertoire against Epstein-Barr virus (EBV), once established following primary infection, exhibits a robust stability over time. However, the determinants contributing to this long-term persistence are still poorly characterized. Taking advantage of an in vivo clinical setting where lymphocyte homeostasis was transiently perturbed, we studied EBV antigen-specific CD8 T cells before and after non-myeloablative lympho-depleting chemotherapy of melanoma patients. Despite more advanced T cell differentiation, patients T cells showed clonal composition comparable to healthy individuals, sharing a preference for TRBV20 and TRBV29 gene segment usage and several co-dominant public TCR clonotypes. Moreover, our data revealed the presence of relatively few dominant EBV antigen-specific T cell clonotypes, which mostly persisted following transient lympho-depletion (TLD) and lymphocyte recovery, likely related to absence of EBV reactivation and de novo T cell priming in these patients. Interestingly, persisting clonotypes frequently co-expressed memory/homing-associated genes (CD27, IL7R, EOMES, CD62L/SELL and CCR5) supporting the notion that they are particularly important for long-lasting CD8 T cell responses. Nevertheless, the clonal composition of EBV-specific CD8 T cells was preserved over time with the presence of the same dominant clonotypes after non-myeloablative chemotherapy. The observed clonotype persistence demonstrates high robustness of CD8 T cell homeostasis and reconstitution.
authors.affiliation: Department of Oncology, Lausanne University Hospital Center (CHUV) and University of Lausanne, Lausanne, Switzerland.
authors.forename: Emanuela M
authors.initials: EM
authors.lastname: Iancu
authors.forename: Philippe O
authors.initials: PO
authors.lastname: Gannon
authors.forename: Julien
authors.initials: J
authors.lastname: Laurent
authors.forename: Bhawna
authors.initials: B
authors.lastname: Gupta
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Olivier
authors.initials: O
authors.lastname: Michielin
authors.forename: Emanuela
authors.initials: E
authors.lastname: Romano
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rufer
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D002999:Clone Cells / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D008545:Melanoma / Q000276:immunology* / Q000821:virology; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D000956:Antigens, Viral; D011948:Receptors, Antigen, T-Cell