High percentage of blood-based T-cell receptor gamma V9-JP recombinations associated with amyotrophic lateral sclerosis: extensive retention of the JP KKIK amino acid motif

G. Blanck, Taha I. Huda, Konrad J. Cios, George Angelakakis, Joanna J Song
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Abstract

Exome and RNAseq files prepared from blood samples can be mined for adaptive immune receptor recombinations and thus for the complementarity determining region-3 (CDR3) amino acid (AA) sequences, important for antigen binding. In this report, the T-cell receptor gamma (TRG) recombinations were mined from amyotrophic lateral sclerosis (ALS) blood sample exome and RNAseq files, mainly inspired by: (i) a high level of gamma-delta T-cells in Parkinson’s disease and (ii) TRG CDR3 AA features associated with a higher Braak stage in Alzheimer’s disease. Results indicated a high percentage of V9-JP recombinations from ALS blood sample genomics files, in comparison to TRG recombinations obtained from a large number of blood and other tissue samples not representing ALS. This result is discussed in the context of potential phospholipid sponging by adaptive immune receptors and potential impacts on membrane rigidity and amyloid development.
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与肌萎缩性脊髓侧索硬化症有关的高比例血源性 T 细胞受体伽马 V9-JP 重组:JP KKIK 氨基酸基序的广泛保留
从血液样本中制备的外显子组和 RNAseq 文件可以挖掘适应性免疫受体重组,从而挖掘对抗原结合非常重要的互补决定区-3(CDR3)氨基酸(AA)序列。本报告从肌萎缩性脊髓侧索硬化症(ALS)血液样本外显子组和 RNAseq 文件中挖掘出了 T 细胞受体 gamma(TRG)重组,主要受到以下启发:(i) 帕金森病中γ-δ T 细胞水平较高,(ii) TRG CDR3 AA 特征与阿尔茨海默病中较高的 Braak 分期相关。结果表明,与从大量血液和其他非 ALS 组织样本中获得的 TRG 重组相比,ALS 血液样本基因组学文件中的 V9-JP 重组比例较高。这一结果将在适应性免疫受体的潜在磷脂海绵化以及对膜刚性和淀粉样蛋白发展的潜在影响的背景下进行讨论。
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