Anichini A, Mortarini R, Maccalli C, Squarcina P, Fleischhauer K, Mascheroni L, Parmiani G
Division of Experimental Oncology D, National Tumor Institute, Milan, Italy.
J Immunol. 1996 Jan 1;156(1):208-17.
To determine whether HLA-A21 restricted melanoma Ags exist that are not expressed on normal melanocytes, a panel of 478 T cell clones from six HLA-A21+ patients was selected for HLA-A2 restricted lysis of autologous tumor and then tested for differential recognition of HLA-A2.1+ melanomas and normal melanocytes. Four subsets of clones were identified in the panel of 107 HLA-A2-restricted CTL clones. CTL clones from three of the four subsets did not lyse melanocytes, but recognized fresh HLA-A2.1+ melanomas and defined three classes of epitopes, including unique Ags, common melanoma Ags, and Ags shared with neoplastic cells of different histologic origin. These CTL clones did not recognize any of the 10 peptides selected for specific association to HLA-A2.1 and derived from Melan-A/Mart-1, tyrosinase, gp100, or MAGE-3 proteins. By contrast, the fourth subset of HLA-A2.1-restricted CTl clones recognized both melanoma and melanocytes. These CTL clones were directed to a peptide from either Melan-A/Mart-1, tyronise, or gp100. By a limiting dilution assay, designed to evaluate the frequency of HLA-A2-restricted CTL precursors (CTLp) directed to melanoma but not to melanocytes, such precursors were found in the peripheral blood or tumor site of five of six HLA-A2.1+ melanoma patients, and their frequency was much higher than the frequency of CTLp recognizing both tumor cells and the melanocytes. These results suggest that in melanoma patients most of the HLA-A2.1-restricted immune repertoire to melanoma is directly to epitopes expressed in the neoplastic but not in the normal cells of the melanocyte lineage.
为了确定是否存在不在正常黑素细胞上表达的HLA - A21限制性黑色素瘤抗原，从6名HLA - A21阳性患者中选取了一组478个T细胞克隆，用于对自体肿瘤进行HLA - A2限制性裂解，然后检测其对HLA - A2.1阳性黑色素瘤和正常黑素细胞的差异识别。在107个HLA - A2限制性CTL克隆组中鉴定出四个克隆亚群。四个亚群中的三个亚群的CTL克隆不裂解黑素细胞，但识别新鲜的HLA - A2.1阳性黑色素瘤，并定义了三类表位，包括独特抗原、常见黑色素瘤抗原以及与不同组织学来源的肿瘤细胞共有的抗原。这些CTL克隆不识别为与HLA - A2.1特异性结合而选择的、源自Melan - A/Mart - 1、酪氨酸酶、gp100或MAGE - 3蛋白的10种肽中的任何一种。相比之下，HLA - A2.1限制性CTL克隆的第四个亚群既识别黑色素瘤也识别黑素细胞。这些CTL克隆针对的是来自Melan - A/Mart - 1、酪氨酸酶或gp100的一种肽。通过有限稀释分析来评估针对黑色素瘤而非黑素细胞的HLA - A2限制性CTL前体（CTLp）的频率，在6名HLA - A2.1阳性黑色素瘤患者中的5名患者的外周血或肿瘤部位发现了此类前体，并且它们的频率远高于识别肿瘤细胞和黑素细胞的CTLp的频率。这些结果表明，在黑色素瘤患者中，大多数针对黑色素瘤的HLA - A2.1限制性免疫库直接针对黑素细胞系肿瘤细胞而非正常细胞中表达的表位。
