Selection of T cell clones expressing high-affinity public TCRs within human cytomegalovirus-specific CD8 T cell responses

Lydie Trautmann, Marie Rimbert, Klara Echasserieau, Xavier Saulquin, Bérangère Neveu, Julie Dechanet, Vincenzo Cerundolo, Marc Bonneville

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

Assessment of clonal diversity of T cell responses against human CMV (HCMV), a major cause of morbidity in immunodepressed patients, provides important insights into the molecular basis of T cell immunodominance, and has also clinical implications for the immunomonitoring and immunotherapy of HCMV infections. We performed an in-depth molecular and functional characterization of CD8 T cells directed against an immunodominant HLA-A2-restricted epitope derived from HCMV protein pp65 (NLV/A2) in steady state and pathological situations associated with HCMV reactivation. NLV/A2-specific T cells in healthy HCMV-seropositive donors showed limited clonal diversity and usage of a restricted set of TCR Vβ regions. Although TCRβ-chain junctional sequences were highly diverse, a large fraction of NLV/A2-specific T cells derived from distinct individuals showed several recurrent (so-called "public") TCR features associated in some cases with full conservation of the TCRα chain junctional region. A dramatic clonal focusing of NLV/A2-specific T cells was observed in situations of HCMV reactivation and/or chronic inflammation, which resulted in selection of a single clonotype displaying similar public TCR features in several patients. In most instances the NLV/A2-specific dominant clonotypes showed higher affinity for their Ag than subdominant ones, thus suggesting that TCR affinity/avidity is the primary driving force underlying repertoire focusing along chronic antigenic stimulation.

Original languageEnglish (US)
Pages (from-to)6123-6132
Number of pages10
JournalJournal of Immunology
Volume175
Issue number9
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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