A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope
A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope
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DOI：
10.1007/s00262-012-1284-7
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发表时间：
2012-12-01
影响因子：
5.8
通讯作者：
Celis, Esteban
中科院分区：
文献类型：
--
作者：
Kobayashi, Hiroya;Kumai, Takumi;Celis, Esteban
人类T细胞白血病病毒1型（HTLV-1）诱导的成人T细胞白血病/淋巴瘤（ATLL）是一种致死性淋巴组织增生性恶性疾病。因此，通过使用特征化的T细胞肽表位开发治疗性疫苗来增强对ATLL的T细胞免疫可能是有价值的。我们分离和表征HLA-DR结合的肽HTLV-1转化的T细胞通过分级反相高效液相色谱和Edman NH 2-末端测序，并能够确定五个独立的肽序列。鉴定的肽序列之一对应于人白细胞介素-9受体α（IL-9 R α）的片段，其通常由HTLV-1感染的T细胞淋巴瘤细胞表达。利用与已鉴定的IL-9 R α序列相对应的合成肽，我们在体外产生了抗原特异性的CD 4辅助性T淋巴细胞，其被HLA-DR 15或HLA-DR 53分子限制，并且可以识别和杀伤HTLV-1+、IL-9 R α + T细胞淋巴瘤细胞。这些结果表明，IL-9 R α作为CD 4 T细胞的T细胞白血病/淋巴瘤相关抗原发挥作用，并且合成肽如本文所述的合成肽可用于针对IL-9 R α阳性ATLL的基于T细胞的免疫疗法。
Human T cell leukemia virus type 1 (HTLV-1) induced adult T cell leukemia/lymphoma (ATLL) is usually a fatal lymphoproliferative malignant disease. Thus, the enhancement of T cell immunity to ATLL through the development of therapeutic vaccines using characterized T cell peptide epitopes could be of value. We isolated and characterized HLA-DR-bound peptides from HTLV-1-transformed T cells by fractionating on reverse-phase high performance liquid chromatography and Edman NH2-terminal sequencing and were able to identify five independent peptide sequences. One of the identified peptide sequences corresponded to a fragment of the human interleukin-9 receptor alpha (IL-9R alpha), which is commonly expressed by HTLV-1-infected T cell lymphoma cells. Using a synthetic peptide corresponding to the identified IL-9R alpha sequence, we generated antigen-specific CD4 helper T lymphocytes in vitro, which were restricted by HLA-DR15 or HLA-DR53 molecules and could recognize and kill HTLV-1+, IL-9R alpha+ T cell lymphoma cells. These results indicate that IL-9R alpha functions as T cell leukemia/lymphoma-associated antigen for CD4 T cells and that synthetic peptides such as the one described here could be used for T cell-based immunotherapy against IL-9R alpha positive ATLL.