期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep44661
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资金
- Kompetenznetz Diabetes Mellitus (Competence Network for Diabetes Mellitus) - Federal Ministry of Education and Research [FKZ 01GI0805]
- Juvenile Diabetes Research Foundation (JDRF) [JDRF-No17-2012-16]
- German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research
- JDRF [3-PDF-2016-188-A-N]
- DFG Research Center and Cluster of Excellence-Center for Regenerative Therapies Dresden [FZ 111]
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 IGRP(265-273) 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 alpha-and beta-chain sequences of 418 patient-derived IGRP(265-273)-multimer(+) CD8(+) T cells representing 48 clonotypes were obtained. Expanded populations of IGRP(265-273)-specific CD8(+) T cells with dominant clonotypes that had TCR alpha-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 alpha-chain sequencing, we found enrichment of one of these TCR alpha-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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