Chen Z W, Li Y, Zeng X, Kuroda M J, Schmitz J E, Shen Y, Lai X, Shen L, Letvin N L
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
J Immunol. 2001 Apr 1;166(7):4525-33. doi: 10.4049/jimmunol.166.7.4525.
The TCR repertoire of an epitope-specific CD8(+) T cell population remains poorly characterized. To determine the breadth of the TCR repertoire of a CD8(+) T cell population that recognizes a dominant epitope of the AIDS virus, the CD8(+) T cells recognizing the tetrameric Mamu-A01/p11C(,CM) complex were isolated from simian immunodeficiency virus (SIV)-infected Mamu-A01(+) rhesus monkeys. This CD8(+) T cell population exhibited selected usage of TCR V beta families and complementarity-determining region 3 (CDR3) segments. Although the epitope-specific CD8(+) T cell response was clearly polyclonal, a dominance of selected V beta(+) cell subpopulations and clones was seen in the TCR repertoire. Interestingly, some of the selected V beta(+) cell subpopulations and clones maintained their dominance in the TCR repertoire over time after infection with SIV of macaques. Other V beta(+) cell subpopulations declined over time in their relative representation and were replaced by newly evolving clones that became dominant. The present study provides molecular evidence indicating that the TCR repertoire shaped by a single viral epitope is dominated at any point in time by selected V beta(+) cell subpopulations and clones and suggests that dominant V beta(+) cell subpopulations and clones can either be stable or evolve during a chronic infection.
表位特异性CD8(+) T细胞群体的TCR库仍然缺乏充分的特征描述。为了确定识别艾滋病病毒主要表位的CD8(+) T细胞群体的TCR库广度,从感染猿猴免疫缺陷病毒(SIV)的Mamu-A01(+)恒河猴中分离出识别四聚体Mamu-A01/p11C(,CM)复合物的CD8(+) T细胞。该CD8(+) T细胞群体表现出TCR Vβ家族和互补决定区3(CDR3)片段的选择性使用。尽管表位特异性CD8(+) T细胞反应明显是多克隆的,但在TCR库中可见特定Vβ(+)细胞亚群和克隆的优势。有趣的是,在猕猴感染SIV后的一段时间内,一些选定的Vβ(+)细胞亚群和克隆在TCR库中保持其优势地位。其他Vβ(+)细胞亚群的相对比例随时间下降,并被新出现的占主导地位的克隆所取代。本研究提供了分子证据,表明由单一病毒表位塑造的TCR库在任何时间点都由选定的Vβ(+)细胞亚群和克隆主导,并表明占主导地位的Vβ(+)细胞亚群和克隆在慢性感染期间既可以稳定也可以进化。