Mannering S I, McKenzie J L, Fearnley D B, Hart D N
Haematology/Immunology Research Group, Christchurch Hospital, New Zealand.
Blood. 1997 Jul 1;90(1):290-7.
Chronic myeloid leukemia (CML) is characterized by a specific translocation of the c-abl oncogene on chromosome 9 to the break point cluster region (bcr) on chromosome 22, t(9;22) (q34;q11). This translocation results in the expression of a 210-kD bcr-abl protein fusion gene product. The juxtaposition of the bcr and abl genes produces a novel junctional amino acid sequence, which may be presented by antigen-presenting cells and recognized specifically by human T lymphocytes. We have generated a CD4+ T lymphocyte line (NG-1) which recognizes the peptide epitope (GFKQSSKALQR) in association with HLA-DRbeta1*0101-02. A comparison of antigen-presenting cells showed that CMRF-44+ blood dendritic cell presented a 12mer b3a2 peptide effectively. The b3a2 peptide was able to generate specific primary T-lymphocyte responses in other HLA-DR1 donors. We also show that bcr-abl, b3a2 peptide-specific T-lymphocyte lines proliferate in response to bcr-abl b3a2 containing cell lysates (K562 or CML PBMC derived) but not control (including b2a2 CML PBMC) lysates.
慢性粒细胞白血病（CML）的特征是9号染色体上的c-abl癌基因特异性易位至22号染色体的断裂点簇区域（bcr），即t(9;22) (q34;q11)。这种易位导致一种210-kD的bcr-abl蛋白融合基因产物的表达。bcr和abl基因的并列产生了一种新的连接氨基酸序列，该序列可能由抗原呈递细胞呈递，并被人类T淋巴细胞特异性识别。我们已经建立了一种CD4+ T淋巴细胞系（NG-1），它能识别与HLA-DRbeta1*0101-02相关的肽表位（GFKQSSKALQR）。抗原呈递细胞的比较显示，CMRF-44+血液树突状细胞能有效呈递一种12聚体b3a2肽。b3a2肽能够在其他HLA-DR1供体中产生特异性的初始T淋巴细胞反应。我们还表明，bcr-abl、b3a2肽特异性T淋巴细胞系在含有bcr-abl b3a2的细胞裂解物（源自K562或CML PBMC）刺激下增殖，但在对照（包括b2a2 CML PBMC）裂解物刺激下不增殖。
