Posnett D N, Vissinga C S, Pambuccian C, Wei S, Robinson M A, Kostyu D, Concannon P
Department of Medicine, Cornell University Medical College, New York 10021.
J Exp Med. 1994 May 1;179(5):1707-11. doi: 10.1084/jem.179.5.1707.
One of the causes of variations in the expressed human T cell receptor (TCR) BV (V beta) repertoire is genetic variation in the germline DNA. Herein evidence is provided that allelic polymorphism may affect recombination frequency for a specific V gene. Two alleles of the TCR BV3 differ only at a single nucleotide position (C/T) within the 23-bp spacer region of the recombination signal sequence. These alleles are associated with variable percentages of BV3 cells in the peripheral blood, as shown in families and in unrelated normal donors. Individuals homozygous for allele 2 have a mean of 8.1% BV3 cells, heterozygous individuals have a mean of 4.7% BV3 cells, and homozygotes for allele 1 have a mean of 1.2% BV3 cells in CD3+ CD4+ peripheral blood T cells. Since the correlation is tight in unrelated individuals and other genetic differences were not found in the vicinity of BV3, we suggest that the spacer region sequence itself modifies recombination efficiency. This allelic system provides an example of a novel mechanism by which cis-acting genetic elements may affect recombination in a natural in vivo system.
人类T细胞受体（TCR）BV（Vβ）表达谱变异的原因之一是种系DNA中的基因变异。本文提供的证据表明，等位基因多态性可能影响特定V基因的重组频率。TCR BV3的两个等位基因仅在重组信号序列23bp间隔区的单个核苷酸位置（C/T）存在差异。如在家族成员和无关正常供体中所示，这些等位基因与外周血中BV3细胞的不同百分比相关。在CD3 + CD4 +外周血T细胞中，等位基因2的纯合个体BV3细胞平均占8.1%，杂合个体平均占4.7%，等位基因1的纯合个体平均占1.2%。由于在无关个体中这种相关性紧密，且在BV3附近未发现其他基因差异，我们认为间隔区序列本身会改变重组效率。这个等位基因系统提供了一个新机制的例子，即顺式作用遗传元件可能在天然体内系统中影响重组。
