title: Large TCR diversity of virus-specific CD8 T cells provides the mechanistic basis for massive TCR renewal after antigen exposure.
abstract: Ex vivo analysis of virus-specific CD8 T cell populations by anchored PCR has shown that the CD8 TCR repertoire was less oligoclonal (seven to nine clonotypes per individual epitope) than previously thought. In the current study, TCR diversity was investigated by assessing both the overall TCR β-chain variable regions usage as well as the CDR3 regions in ex vivo-isolated CMV- and EBV-specific CD8 T cells from 27 healthy donors. The average number of clonotypes specific to most single viral epitopes comprised between 14 and 77. Changes in the CD8 TCR repertoire were also longitudinally assessed under conditions of HIV-1 chronic infection (i.e., in patients with suppressed virus replication and after treatment interruption and Ag re-exposure). The results showed that a large renewal (≤ 80%) of the TRB repertoire occurred after Ag re-exposure and was eventually associated with an increased T cell recognition functional avidity. These results demonstrate that the global CD8 TCR repertoire is much more diverse (≤ 9-fold) than previously estimated and provide the mechanistic basis for supporting massive repertoire renewal during chronic virus infection and Ag re-exposure.
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, University Hospital Center, University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miconnet
authors.forename: Angélique
authors.initials: A
authors.lastname: Marrau
authors.forename: Alex
authors.initials: A
authors.lastname: Farina
authors.forename: Patrick
authors.initials: P
authors.lastname: Taffé
authors.forename: Selena
authors.initials: S
authors.lastname: Vigano
authors.forename: Alexandre
authors.initials: A
authors.lastname: Harari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
mesh_terms: D000940:Antigenic Variation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D011948:Receptors, Antigen, T-Cell