Zarour H M, Storkus W J, Brusic V, Williams E, Kirkwood J M
Department of Medicine and Melanoma Center, University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA.
Cancer Res. 2000 Sep 1;60(17):4946-52.
The NY-ESO-1 gene is expressed by a range of human tumors and encodes HLA-A2-restricted melanoma peptides recognized by CD8+ CTLs. Here we report that the NY-ESO-1 gene also encodes two overlapping, but non-cross-reactive, HLA-DRB10401-presented peptides that are recognized by CD4+ T cells. The NY-ESO-1(119-143) peptide was able to induce specific CD4+ T cells in vitro from both an HLA-DRB10401+ normal donor and an HLA-DRB10401+ patient with melanoma. Bulk and cloned CD4+ T cells produced IFN-gamma specifically in response to, and also lysed, T2.DR4 cells pulsed with peptide NY-ESO-1(119-143) and the autologous tumor cell line, but not a DRB10401+ melanoma cell line that does not express NY-ESO-1. Interestingly, the NY-ESO119-143 peptide contains two overlapping putative "core" epitopes recognized by non-cross-reactive anti-NY-ESO-1(119-143) CD4+ T-cell clones. Taken together, these data support the use of this novel DR4-restricted tumor peptide, NY-ESO-1(119-143), or its two "sub-epitopes" in immunotherapeutic trials designed to generate or enhance specific CD4+ T-cell responses against tumors expressing NY-ESO-1 in vivo.
NY-ESO-1基因在多种人类肿瘤中表达，并编码可被CD8+细胞毒性T淋巴细胞（CTL）识别的HLA-A2限制性黑色素瘤肽段。在此我们报告，NY-ESO-1基因还编码两种重叠但无交叉反应性、由HLA-DRB10401呈递的肽段，它们可被CD4+ T细胞识别。NY-ESO-1(119 - 143)肽段能够在体外从HLA-DRB10401+正常供体和HLA-DRB10401+黑色素瘤患者中诱导出特异性CD4+ T细胞。大量及克隆的CD4+ T细胞在受到肽段NY-ESO-1(119 - 143)和自体肿瘤细胞系刺激时，会特异性产生γ干扰素，同时还能裂解用该肽段脉冲处理的T2.DR4细胞，但不能裂解不表达NY-ESO-1的DRB10401+黑色素瘤细胞系。有趣的是，NY-ESO119 - 143肽段包含两个重叠的假定“核心”表位，可被无交叉反应性的抗NY-ESO-1(119 - 143) CD4+ T细胞克隆识别。综上所述，这些数据支持在旨在体内产生或增强针对表达NY-ESO-1肿瘤的特异性CD4+ T细胞反应的免疫治疗试验中使用这种新型的DR4限制性肿瘤肽段NY-ESO-1(119 - 143)或其两个“亚表位”。
