Clonotype selection and composition of human CD8 T cells specific for persistent herpes viruses varies with differentiation but is stable over time.

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State: Public
Version: Final published version
Serval ID
serval:BIB_33495AFDDE88
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Clonotype selection and composition of human CD8 T cells specific for persistent herpes viruses varies with differentiation but is stable over time.
Journal
Journal of immunology
Author(s)
Iancu E.M., Corthesy P., Baumgaertner P., Devevre E., Voelter V., Romero P., Speiser D.E., Rufer N.
ISSN
1550-6606
Publication state
Published
Issued date
06/2009
Peer-reviewed
Oui
Volume
183
Number
1
Pages
319-331
Language
english
Abstract
Protection from reactivation of persistent herpes virus infection is mediated by Ag-specific CD8 T cell responses, which are highly regulated by still poorly understood mechanisms. In this study, we analyzed differentiation and clonotypic dynamics of EBV- and CMV-specific T cells from healthy adults. Although these T lymphocytes included all subsets, from early-differentiated (EM/CD28(pos)) to late-differentiated (EMRA/CD28(neg)) stages, they varied in the sizes/proportions of these subsets. In-depth clonal composition analyses revealed TCR repertoires, which were highly restricted for CMV- and relatively diverse for EBV-specific cells. Virtually all virus-specific clonotypes identified in the EMRA/CD28(neg) subset were also found within the pool of less differentiated "memory" cells. However, striking differences in the patterns of dominance were observed among these subsets, because some clonotypes were selected with differentiation while others were not. Late-differentiated CMV-specific clonotypes were mostly characterized by TCR with lower dependency on CD8 coreceptor interaction. Yet all clonotypes displayed similar functional avidities, suggesting a compensatory role of CD8 in the clonotypes of lower TCR avidity. Importantly, clonotype selection and composition of each virus-specific subset upon differentiation was highly preserved over time, with the presence of the same dominant clonotypes at specific differentiation stages within a period of 4 years. Remarkably, clonotypic distribution was stable not only in late-differentiated but also in less-differentiated T cell subsets. Thus, T cell clonotypes segregate with differentiation, but the clonal composition once established is kept constant for at least several years. These findings reveal novel features of the highly sophisticated control of steady state protective T cell activity in healthy adults.
Keywords
Adult, CD8-Positive T-Lymphocytes/classification, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/chemical synthesis, Cancer Vaccines/genetics, Cell Aging/genetics, Cell Aging/immunology, Cell Differentiation/genetics, Cell Differentiation/immunology, Cells, Cultured, Clone Cells, Cytomegalovirus/immunology, Cytomegalovirus/pathogenicity, Cytomegalovirus Infections/immunology, Cytomegalovirus Infections/prevention & control, Epitopes, T-Lymphocyte/chemistry, Epitopes, T-Lymphocyte/genetics, Epstein-Barr Virus Infections/immunology, Epstein-Barr Virus Infections/prevention & control, Gene Expression Regulation, Viral/immunology, Herpesvirus 4, Human/immunology, Herpesvirus 4, Human/pathogenicity, Herpesvirus Vaccines/chemical synthesis, Herpesvirus Vaccines/genetics, Humans, Middle Aged, Phosphoproteins/chemistry, Phosphoproteins/genetics, Receptors, Antigen, T-Cell/chemistry, Receptors, Antigen, T-Cell/genetics, Receptors, Antigen, T-Cell, alpha-beta/chemistry, Receptors, Antigen, T-Cell, alpha-beta/genetics, Time Factors, Trans-Activators/chemistry, Trans-Activators/genetics, Viral Matrix Proteins/chemistry, Viral Matrix Proteins/genetics
Pubmed
Web of science
Open Access
Yes
Create date
16/09/2009 12:04
Last modification date
20/08/2019 13:19
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