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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 果伽蘭 | |
| dc.contributor.author | Huei-Jhen Li | en |
| dc.contributor.author | 李慧真 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:16:37Z | - |
| dc.date.available | 2011-07-27 | |
| dc.date.copyright | 2006-07-27 | |
| dc.date.issued | 2005 | |
| dc.date.submitted | 2006-07-24 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32830 | - |
| dc.description.abstract | 人類T 細胞接受器α鏈，保守估計至少有4.5 × 105 種完全不同序列，變異性相當的高[1]，然而發現了不同人都具有相同序列的T細胞接受器α基因，稱為不變T細胞接受器(invariant TCR)後，研究者注意到這種可能帶有重要的調控功能的T細胞接受器。目前已知的不變T細胞接受器有兩條，第一條是在人類和老鼠體內NK細胞T細胞接受器上所表現的Vα24Jα18。第二條同樣在老鼠和人類體內都可發現類似的序列，基因組合為Vα1Jα33。而我們發現了第三條屬於人之間的不變T細胞接受器，為Vα1Jα12所組成，這條不變的T細胞接受器可以在不同的人及不同的組織中都偵測到，我們也發現，這條不變T細胞接受器和第二條不變T細胞接受器有相同也有相異處。相同的地方是他們T細胞接受器的CDR3胺基酸序列非常相似；不同的地方則是人類或老鼠的腸道中會有許多表現第二條不變T細胞接受器的T細胞聚集，但是並沒有在人類的腸道中偵測到Vα1Jα12這條不變T細胞接受器。
V(D)J重組的分子機轉目前都還不是很清楚，而我們由實驗室的所定序的三千五百三十八條及GeneBank公佈的九百四十九條人類T細胞接受器α鏈的序列中發現，在人類六十一個Jαs當中有八個完全沒有被使用，我們稱之為T細胞接受器α鏈基因重組的冷區(cold spot)，分別是Jα1、2、14、25、51、55、59和60。我們經由重組訊號序列 (recombination signal sequence)分析、germline transcripts偵測和組蛋白H3及H4乙烯基化的分析實驗，去幫助了解在生物體中，T細胞接受器α鏈的V到J重組過程的分子調控機轉。 | zh_TW |
| dc.description.abstract | T cells recognize antigens as peptides presented in the context of MHC class I or class II molecules with the fine specificity that is defined by the TCR. The majority of T cells express the TCR composed of disulfide-linked αβ heterodimer. Arstila et al. [1] estimated an average diversity of 4.5×105 different chains in the human naïve T cell repertoire. Regardless the calculated complexity, two invariant TCR α chains have been identified documented to be conserved among species. The first one is encoded by Vα24Jα18 and expressed on subset of NKT cells. The second one is encoded by Vα1Jα33. Here we report the finding of the third invariant TCR α chain, Vα1-Jα12 in humans.
The mechanisms regulating V-to-Jα recombination remain elusive. We found eight Jα segments, Jα1, 2, 14, 25, 51, 55, 59, and 60, that were not used in vivo in a cohort of 4,487 TCR α chain sequences. We call these Jαs as recombination cold spots. Histone acetylation, germline transcript and RSS were analyzed on these cold spots to understand the molecular mechanism regulating the in vivo process of V-to-Jα rearrangement. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:16:37Z (GMT). No. of bitstreams: 1 ntu-94-R93b46021-1.pdf: 780648 bytes, checksum: d0896fc55e36fb8aa32b44b15823c69b (MD5) Previous issue date: 2005 | en |
| dc.description.tableofcontents | Content i
List of figure iii List of table iv 中文摘要 v Abstract vi List of abbreviation vii .Introduction 1 1.1 Immune system[1] 1 1.2 B and T lymphocytes 2 1.2.1 B lymphocytes 2 1.2.2 T lymphocytes 3 1.2.3 B and T interaction 5 1.3 TCR, Ag, and MHC 5 1.3.1 TCR 5 1.3.3 TCR gene rearrangement 7 1.3.4 Computational tools for analysis of Jα RSS 10 1.3.5 Invariant TCR 12 Material and Method 14 2.1 Material 14 2.1.1 Thymus 14 2.1.2 PBL (peripheral blood lymphocytes) 14 2.1.3 cDNA from various human tissues 14 2.2 Method 14 2.2.1 Isolation of thymocyte subpopulations 14 2.2.2 Isolation of PBL subpopulations 15 2.2.3 Isolation of β7+ and β7- lymphocytes from human PBL 15 2.2.4 Genomic DNA isolation 16 2.2.5 RT-PCR and Germline transcription 16 2.2.6 ChIP (chromatin immunoprecipitation) 16 2.2.7 Ligation-mediated PCR 18 2.2.8 Cloning 18 2.2.8.1 DNA ligation 18 2.2.8.2 Transformation 18 2.2.8.3 Colony PCR 19 2.2.8.4 Agarose Gel Electrophoresis 20 2.2.9 DNA sequencing 20 2.2.9.1 Cycle Reaction 20 2.2.9.2 Polyacrylamide Gel Electrophoresis 21 2.2.9.3 Autosequencing 21 Result 22 3.1 The invariant TCR studies 22 3.1.1 Detection of the third invariant TCR 22 3.1.2 Detection of invariant Vα1-Jα12 TCR in β7+ and β7- PBLs 23 3.2.1 Detection of cold spot Jαs usage from cDNA 24 3.2.2 Detection of cold spot Jαs usage from genomic DNA 24 3.2.3 Analysis of histone H3/H4 acetylation at cold spot Jαs loci 25 3.2.4 Cold spot Jαs germline transcript detection 25 3.2.5 Sequence analysis of Cold Jα RSS 26 3.2.6 Computational analysis of Jα RSS 26 3.2.7 Double strand break can be detected on Vα1 coding end 28 Discussion 29 4.1 The third invariant TCR 29 4.2 Regulation of recombination 30 Reference 32 | |
| dc.language.iso | en | |
| dc.subject | 接受器 | zh_TW |
| dc.subject | α鏈 | zh_TW |
| dc.subject | 不變T細胞接受器 | zh_TW |
| dc.subject | T細胞 | zh_TW |
| dc.subject | T cell receptor α chain | en |
| dc.subject | invariant TCR | en |
| dc.title | 人類T細胞接受器基因使用的研究顯示(1)第三個不變T細胞接受器α鏈基因及(2)調控生物體內V到Jα重組過程的分子機轉 | zh_TW |
| dc.title | Human T cell receptor (TCR) gene usage studies reveal (i) a third invariant TCR α gene and (ii) the molecular mechanism regulating the in vivo process of V-to-Jα rearrangement | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王惠鈞,張金堅,陳義雄,陳水田 | |
| dc.subject.keyword | T細胞,接受器,不變T細胞接受器,α鏈, | zh_TW |
| dc.subject.keyword | T cell receptor α chain,invariant TCR, | en |
| dc.relation.page | 56 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-25 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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