Nakao Shinji
Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Japan.
Int J Hematol. 2002 Aug;76 Suppl 1:274-6. doi: 10.1007/BF03165261.
In an attempt to identify novel mHas that induce GVL effect on chronic myeloid leukemia (CML), we analyzed peripheral blood T cells of 4 CML patients who relapsed after allogeneic stem cell transplantation and received donor leukocyte infusion (DLI), for the presence of antigen-specific T-cell proliferation. When peripheral blood lymphocyte collected from patients every 2-4 weeks after DLI were subjected to complementarity determining region (CDR) 3 size distribution analysis of T-cell receptor beta chain, clonal proliferation of a limited number of CD4+ T cells was detected in all patients 2-4 months after DLI in association with the occurrence of GVL effect. To identify an epitope of the T-cell clone that probably mediates GVL effect, we determined nucleotide sequence of CDR3 of the T cells and screened the database for the presence of T cells with a CDR3 sequence similar to that of the GVL-mediating T cells. In one of 4 patients who showed clonal proliferation of a BV16+ T cell, a CDR3 motif QDR was shared by a T-cell clone that recognized an 85-99 peptide of myelin basic protein presented by HLA-DRB11501. When the I domain of CD49b, a candidate peptides that could bind to this CDR3 motif in the context of DRB11501, was studied, codon 256 in the I domain of the recipient was ATT (Ile) while that of the donor was GTT (Val). The BV16+ T cells showed proliferative response to DRB1*1501 L-cell transfectant pulsed with the recipient type CD49b. Thus, identification of a clonotype of T cells that mediate GVL effect in patients receiving DLI and a search for T-cell clones with a similar clonotype to the GVL-mediating T cells followed by screening of polymorphic peptides that could stimulate the T cells appears to be useful in identifying novel mHas serving a target antigens of GVL effect.
为了鉴定对慢性髓性白血病（CML）具有移植物抗白血病（GVL）效应的新型微小同种异体抗原（mHas），我们分析了4例异基因干细胞移植后复发并接受供体白细胞输注（DLI）的CML患者的外周血T细胞，以检测抗原特异性T细胞增殖情况。当在DLI后每2 - 4周从患者采集的外周血淋巴细胞进行T细胞受体β链互补决定区（CDR）3大小分布分析时，在所有患者中，DLI后2 - 4个月检测到有限数量的CD4 + T细胞克隆性增殖，且与GVL效应的出现相关。为了鉴定可能介导GVL效应的T细胞克隆的表位，我们测定了T细胞CDR3的核苷酸序列，并在数据库中筛选具有与介导GVL的T细胞相似CDR3序列的T细胞。在4例显示BV16 + T细胞克隆性增殖的患者中，一个识别由HLA - DRB1 * 1501呈递的髓鞘碱性蛋白85 - 99肽段的T细胞克隆共享了一个CDR3基序QDR。当研究在DRB1 * 1501背景下可能与该CDR3基序结合的候选肽CD49b的I结构域时，受体的I结构域中的第256密码子为ATT（异亮氨酸），而供体的为GTT（缬氨酸）。BV16 + T细胞对用受体型CD49b脉冲处理的DRB1 * 1501 L细胞转染体表现出增殖反应。因此，鉴定接受DLI患者中介导GVL效应的T细胞克隆型，寻找与介导GVL的T细胞具有相似克隆型的T细胞克隆，随后筛选可刺激这些T细胞的多态性肽段，似乎有助于鉴定作为GVL效应靶抗原的新型mHas。
