Measuring T cell receptor and T cell gene expression diversity in antigen-responsive human CD4+ T cells

Anne Eugster, Annett Lindner, Anne Kristin Heninger, Carmen Wilhelm, Sevina Dietz, Mara Catani, Anette G. Ziegler, Ezio Bonifacio

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


T cells have diversity in TCR, epitope recognition, and cytokine production, and can be used for immune monitoring. Furthermore, clonal expansion of TCR families in disease may provide opportunities for TCR-directed therapies. We developed methodology for sequencing expressed genes of TCR alpha and beta chains from single cells and applied this to vaccine (tetanus-toxoid)-responsive CD4+ T cells. TCR alpha and beta chains were both successfully sequenced in 1309 (43%) of 3038 CD4+ T cells yielding 677 different receptors. TRAV and TRBV gene usage differed between tetanus-toxoid-responsive and non-responsive cells (p=0.004 and 0.0002), and there was extensive TCR diversity in tetanus-toxoid-responsive cells within individuals. Identical TCRs could be recovered in different samples from the same subject: TCRs identified after booster vaccination were frequent in pre-booster memory T cells (31% of pre-booster TCR), and also identified in pre-booster vaccination naïve cells (6.5%). No TCR was shared between subjects, but tetanus toxoid-responsive cells sharing one of their TCR chains were observed within and between subjects. Coupling single-cell gene expression profiling to TCR sequencing revealed examples of distinct cytokine profiles in cells bearing identical TCR. Novel molecular methodology demonstrates extensive diversity of Ag-responsive CD4+ T cells within and between individuals.

Original languageEnglish
Pages (from-to)13-22
Number of pages10
JournalJournal of Immunological Methods
Issue number1
StatePublished - 2013
Externally publishedYes


  • Gene expression
  • Human
  • T cell receptor
  • T cells


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