Identifying DNA polymorphisms in human TCRA/D variable genes by direct sequencing of PCR products-猫眼课题宝

通过 PCR 产物直接测序鉴定人类 TCRA/D 可变基因中的 DNA 多态性

DOI：

10.1007/s002510050099

发表时间：

1996

期刊：

Immunogenetics

影响因子：

3.2

通讯作者：

中科院分区：

医学4区

文献类型：

作者：

C. Boysen;C. Carlson;E. Hood;L. Hood;D. Nickerson

t细胞受体（TCR）是一种高度可变的分子，由两条多肽链组成，在主要组织相容性复合体（MHC）分子的背景下识别抗原肽。在这项研究中，我们描述了一种基于序列的人类TCRA/D位点可变(V)基因片段种系多态性搜索。从6 ~ 8个不相关的个体中扩增出30个不同的V基因片段，并从低熔点琼脂糖中测序。在15个V基因片段中鉴定出27个多态性。这些多态性主要是单核苷酸替换，但也有插入/删除多态性和可变长度的单二核苷酸重复。在编码区发现的15个序列变异中，6个是沉默的，9个编码氨基酸变化。所有的氨基酸变化都在非保守残基上发现，通常在高变区，在那里它们可能影响MHC和/或肽识别。因此，TCR基因的种系变异可能会影响个体的免疫反应，也可能导致对自身免疫等疾病的易感性。

Abstract The T-cell receptor (TCR) is a highly variable molecule composed of two polypeptide chains that recognize antigenic peptides in the context of major histocompatibility complex (MHC) molecules. In this study, we describe a sequence-based search for germline polymorphisms in the variable (V) gene segments of the human TCRA/D locus. Thirty different V gene segments were amplified from six to eight unrelated individuals and sequenced from low melting point agarose. Twenty-seven polymorphisms were identified in 15 V gene segments. These polymorphisms are mainly single nucleotide substitutions, but an insertion/deletion polymorphism and a single dinucleotide repeat with variable length were also seen. Of the 15 sequence variations found in the coding regions, six are silent and nine encode amino acid changes. All of the amino acid changes are found at non-conserved residues, frequently in the hypervariable regions, where they may influence MHC and/or peptide recognition. Therefore, it is possible that germline variations in TCR genes could influence an individual’s immune response, and may also contribute to susceptibility to diseases such as autoimmunity.