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目的:探讨p210bcr-abl抗原的免疫原性,预测并鉴定该蛋白来源的HLA-A2限制性T细胞表位,并在慢性粒细胞白血病患者中检测其特异性CTL细胞分布。方法:首先利用生物信息学软件预测并选取2个p210bcr-abl来源的表位:BCR-ABL642与BCR-ABL926m;T2细胞亲和力实验鉴定短肽与HLA-A2分子的亲和力;然后制备分别锚合这2种表位的可溶性HLA-A2四聚体,流式检测术检测其特异性CTL细胞在CML患者外周血CD8+T细胞中的频率。结果:与健康人群相比,BCR-ABL642和BCR-ABL926m肽表位限制性CTL细胞的频率在CML患者均明显升高(P<0.01);而来自流感病毒短肽的特异性CTL细胞在两个群体中无统计学差异(P>0.05);另外,BCR-ABL642特异性CTL细胞的频率在CML慢性期和急变期之间有统计学差异(P<0.05)。结论:所选2种肽表位均具有免疫原性,可建立基于这2种短肽的免疫治疗措施。
OBJECTIVE: To investigate the immunogenicity of p210bcr-abl antigen and to predict and identify HLA-A2-restricted T cell epitopes derived from this protein. The distribution of specific CTL cells in patients with chronic myeloid leukemia was determined. METHODS: Two bioinformatics softwares were used to predict and select two epitopes of p210bcr-abl origin: BCR-ABL642 and BCR-ABL926m. The affinity of short peptides and HLA-A2 molecules were confirmed by T2 cell affinity assay. Two kinds of epitopes of soluble HLA-A2 tetramer, flow cytometry detection of specific CTL cells in CML patients with peripheral blood CD8 T cells in the frequency. Results: Compared with healthy controls, the frequency of CTL restricted by BCR-ABL642 and BCR-ABL926m peptide was significantly higher in CML patients (P <0.01), while the specific CTL cells from influenza virus short peptides There was no significant difference between the two groups (P> 0.05). In addition, the frequency of BCR-ABL642-specific CTL cells was significantly different between CML chronic phase and blastic phase (P <0.05). Conclusion: The selected two kinds of peptide epitopes are immunogenic, immunotherapy can be established based on these two kinds of short peptides.