Boysen C, Carlson C, Hood E, Hood L, Nickerson D A
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Immunogenetics. 1996;44(2):121-7.
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.
T细胞受体（TCR）是一种高度可变的分子，由两条多肽链组成，可在主要组织相容性复合体（MHC）分子的背景下识别抗原肽。在本研究中，我们描述了一种基于序列的方法，用于搜索人类TCRA/D基因座可变（V）基因片段中的种系多态性。从六至八名无关个体中扩增出30个不同的V基因片段，并从低熔点琼脂糖中进行测序。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，但也发现了一个插入/缺失多态性和一个长度可变的单二核苷酸重复序列。在编码区发现的15个序列变异中，6个是沉默变异，9个编码氨基酸变化。所有氨基酸变化均出现在非保守残基处，常见于高变区，在这些区域它们可能影响MHC和/或肽的识别。因此，TCR基因的种系变异有可能影响个体的免疫反应，也可能导致自身免疫等疾病的易感性。
