Killian M Scott, Sabado Rachel Lubong, Kilpatrick Stephanie, Hausner Mary Ann, Jamieson Beth D, Yang Otto O
AIDS Institute and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
AIDS. 2005 Jun 10;19(9):887-96. doi: 10.1097/01.aids.0000171402.00372.c2.
Although the epitopic breadth of HIV-1-specific CD8 T lymphocyte (CTL) responses has been described, the T cell receptor (TCR) diversity of virus-specific cells remains poorly defined.
To address this issue, we applied a novel technique for subtractive analysis of the HIV-1-specific CTL repertoire, combining specific deletion of peptide-specific cells by 5-fluorouracil with TCR spectratyping to identify clonal breadth of CTL recognizing individual peptides.
Comprehensive analysis of an infected individual reveals that nine identified HIV-1-specific responses are comprised of at least 38 distinct T-cell clones (ranging from two to 10 distinct clones per epitope).
Given the potentially crucial role of T-cell receptor breadth for viral recognition and avoidance of escape, this subepitopic analysis of CTL may offer an important measure of cellular immunity for pathogenesis and vaccine studies.
尽管已对HIV-1特异性CD8 T淋巴细胞(CTL)反应的表位广度进行了描述,但病毒特异性细胞的T细胞受体(TCR)多样性仍不清楚。
为解决这一问题,我们应用了一种新技术对HIV-1特异性CTL库进行消减分析,即将5-氟尿嘧啶对肽特异性细胞的特异性缺失与TCR谱型分析相结合,以确定识别单个肽的CTL的克隆广度。
对一名感染者的综合分析显示,九个已确定的HIV-1特异性反应由至少38个不同的T细胞克隆组成(每个表位有两个至十个不同的克隆)。
鉴于T细胞受体广度对病毒识别和逃逸避免可能具有关键作用,这种CTL亚表位分析可能为发病机制和疫苗研究提供细胞免疫的重要指标。