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Fuchs, Y.F. ; Eugster, A.* ; Dietz, S. ; Sebelefsky, C. ; Kühn, D.* ; Wilhelm, C.* ; Lindner, A. ; Gavrisan, A.* ; Knoop, J. ; Dahl, A.* ; Ziegler, A.-G. ; Bonifacio, E.

CD8+ T cells specific for the islet autoantigen IGRP are restricted in their T cell receptor chain usage.

Sci. Rep. 7:44661 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
CD8(+) T cells directed against beta cell autoantigens are considered relevant for the pathogenesis of type 1 diabetes. Using single cell T cell receptor sequencing of CD8(+) T cells specific for the IGRP265-273 epitope, we examined whether there was expansion of clonotypes and sharing of T cell receptor chains in autoreactive CD8(+) T cell repertoires. HLA-A*0201 positive type 1 diabetes patients (n = 19) and controls (n = 18) were analysed. TCR α- and β-chain sequences of 418 patient-derived IGRP265-273-multimer(+) CD8(+) T cells representing 48 clonotypes were obtained. Expanded populations of IGRP265-273-specific CD8(+) T cells with dominant clonotypes that had TCR α-chains shared across patients were observed. The SGGSNYKLTF motif corresponding to TRAJ53 was contained in 384 (91.9%) cells, and in 20 (41.7%) patient-derived clonotypes. TRAJ53 together with TRAV29/DV5 was found in 15 (31.3%) clonotypes. Using next generation TCR α-chain sequencing, we found enrichment of one of these TCR α-chains in the memory CD8(+) T cells of patients as compared to healthy controls. CD8(+) T cell clones bearing the enriched motifs mediated antigen-specific target cell lysis. We provide the first evidence for restriction of T cell receptor motifs in the alpha chain of human CD8(+) T cells with specificity to a beta cell antigen.
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Publication type Article: Journal article
Document type Scientific Article
Reviewing status
Institute(s) Institute of Diabetes and Obesity (IDO)
Institute for Pancreatic Beta Cell Research (IPI)
Institute of Diabetes Research Type 1 (IDF)