Department of Hematology and Oncology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
Cancer Immunol Immunother. 2012 Mar;61(3):313-22. doi: 10.1007/s00262-011-1099-y. Epub 2011 Sep 7.
Clinically effective T-cell responses can be elicited by single peptide vaccination with Wilms' tumor 1 (WT1) epitope 126-134 in patients with acute myeloid leukemia (AML). We recently showed that a predominant T-cell receptor (TCR) β chain was associated with vaccine-induced complete remission in an AML patient (patient 1). In this study, we address the question of whether this predominant clone or the accompanying Vβ11 restriction could be found in other AML patients vaccinated with the same WT1 peptide.
For assessment of Vβ usage, cytotoxic T lymphocytes (CTLs) from four vaccinated patients were divided into specific and non-specific by epitope-specific enrichment. Vβ families were quantified in both fractions using reverse transcribed quantitative PCR. Vβ11-positive 'complementary determining region 3' (CDR3) sequences were amplified from these samples, from bone marrow samples of 17 other vaccination patients, and from peripheral blood of six healthy controls, cloned and sequenced.
We observed a clear bias towards Vβ11 usage of the WT1-specific CTL populations in all four patients. The predominant CDR3β amino acid (AA) sequence of patient 1 was detected in two other patients. CDR3β loops with closely related AA sequences were only found in patient 1. There were no CDR3β AA sequences with side chains of identical chemical properties detected in any patient.
We provide the first data addressing TCR Vβ chain usage in WT1-specific T-cell populations after HLA A*0201-restricted single peptide vaccination. We demonstrate both shared Vβ restriction and the sharing of a TCR β transcript with proven clinical impact in one patient.
在急性髓系白血病（AML）患者中，用 Wilms 肿瘤 1（WT1）表位 126-134 进行单次肽疫苗接种可以引起有效的 T 细胞反应。我们最近表明，在 AML 患者（患者 1）中，与疫苗诱导的完全缓解相关的主要 T 细胞受体（TCR）β链。在这项研究中，我们提出了一个问题，即在接受相同 WT1 肽疫苗接种的其他 AML 患者中，是否可以找到这种主要克隆或伴随的 Vβ11 限制。
为了评估 Vβ 使用情况，将来自四名接种疫苗患者的细胞毒性 T 淋巴细胞（CTL）通过表位特异性富集分为特异性和非特异性。使用逆转录定量 PCR 对两种分数中的 Vβ 家族进行定量。从这些样本、来自 17 名其他接种疫苗患者的骨髓样本和来自 6 名健康对照者的外周血中扩增出 Vβ11 阳性“互补决定区 3”（CDR3）序列，克隆并测序。
我们观察到所有四名患者的 WT1 特异性 CTL 群体中明显偏向于 Vβ11 使用。患者 1 的主要 CDR3β 氨基酸（AA）序列在另外两名患者中被检测到。仅在患者 1 中发现具有密切相关 AA 序列的 CDR3β 环。在任何患者中均未检测到具有相同化学性质侧链的 CDR3β AA 序列。
我们提供了关于 HLA A*0201 限制的单次肽疫苗接种后 WT1 特异性 T 细胞群体中 TCR Vβ 链使用的首个数据。我们证明了在一名患者中既存在共享的 Vβ 限制，又存在具有临床影响的 TCR β 转录本。
