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Eugster, A.* ; Lindner, A.* ; Heninger, A.K.* ; Wilhelm, C.* ; Dietz, S.* ; Ziegler, A.-G. ; Bonifacio, E.*

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

J. Immunol. Methods 400-401, 13-22 (2013)
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Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Human; T cells; T cell receptor; Gene expression; Tcr Repertoire; Single Cells; Beta-chain; Epitope; Alpha; Usage; Quantification; Reconstitution; Recognition; Infection
Reviewing status
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Institute for Pancreatic Beta Cell Research (IPI)