MHC-Ⅰ类分子在肿瘤浸润性淋巴细胞识别人黑色素瘤细胞中的作用

THE ROLE OF MHC Ⅰ MOLECULES IN RECOGNITION OF HUMAN MELANOMA CELLS BY TUMOR INFILTRATING LYMPHOCYTES

应用人白细胞抗原－Ａ２阳性（ＨＬＡ－Ａ＋２）黑色素瘤病人的瘤块中分离得到的肿瘤浸润性淋巴细胞（ＴＩＬ），进行ＨＬＡ－Ａ２限制性ＴＩＬ抗人黑色素瘤细胞作用的研究。在实验中发现，ＴＩＬ对自身和同种异体的ＨＬＡ－Ａ＋２黑色素瘤细胞具有杀伤作用，而对ＨＬＡ－Ａ－２黑色素瘤细胞及ＨＬＡ－Ａ＋２非黑色素瘤细胞无作用。选择重组白细胞介素４（ｒＩＬ－４）＋肿瘤坏死因子α（ＴＮＦα）能促进黑色素瘤细胞ＨＬＡ－Ａ２表达量，并增强ＴＩＬ对瘤细胞的杀伤活性。抗ＣＤ３、抗ＨＬＡ－ＡＢＣ和抗ＨＬＡ－Ａ２单抗具有明显抑制ＴＩＬ的抗瘤细胞活性。结果表明ＴＩＬ杀伤黑色素瘤细胞依赖于Ｔ细胞受体（ＴＣＲ）对瘤细胞共同抗原的识别，并有主要组织相容性复合体－Ⅰ类分子参与。

The melanoma specific cytotoxic T lymphocytes (CTL) lines were derived from the tumor infiltrating lymphocyte(TIL) of HLA A + 2 human melanoma patients,and were used to identify the HLA A 2 molecule as an Ag presenting molecule for melanoma Ag and to kill melanoma by HLA A 2 restricted TIL.These TIL lysed HLA A + 2 autologous and allogeneic melanomas,but not the HLA A - 2 melanomas.They also did not lyse the HLA A + 2 non melanoma cell lines.Autologous and allogeneic melanoma lysis was inhibited by anti CD3,by anti MHC class 1,and by anti HLA A 2 monoclonal antibody.rIL 4 plus TNFα increased the expression of HLA A 2 on melanoma cells,and also enhanced the ability of melanoma cells to stimulate TIL and act as targets of these TIL.The result indicated that the recognition of shared tumor Ag among melanoma cell lines was in a TCR dependent,HLA A 2 restricted manner.