Marincola F M, Shamamian P, Alexander R B, Gnarra J R, Turetskaya R L, Nedospasov S A, Simonis T B, Taubenberger J K, Yannelli J, Mixon A
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1994 Aug 1;153(3):1225-37.
The expression of HLA class I molecules on tumor cells is vital for CD8+T cell recognition of tumor Ags. Loss of HLA class I Ag expression as a result of defective beta 2-microglobulin genes has been described in melanoma cells. To further evaluate mechanisms of tumor escape, HLA class I Ag expression was compared in 24 metastatic melanoma cell lines and 20 melanocyte strains by FACS analysis with use of allele-specific mAbs. Total loss of HLA class I Ag expression was not noted; instead, two relatively common phenomena were identified: 1) A variable degree of expression of HLA-B Ags by melanoma cell lines and melanocytes; however, HLA-A Ags were consistently expressed in all cell types. Furthermore, HLA-B locus Ag expression was detected in vivo in only one of six frozen section specimens obtained from six patients having metastatic melanoma. 2) Loss of allelic expression was noted in two of 14 HLA-A2 (14%) and one of three HLA-A29 (33%) melanoma cell lines and included a full haplotype, which suggests loss of a genomic fragment. Allele-specific PCR amplification demonstrated deletion of genes in linkage disequilibrium within the MHC class II, III, and I regions. Aberrations of HLA class I expression in tumor lines should be considered when assessing MHC-restricted phenomena in in vitro models.
肿瘤细胞上HLA I类分子的表达对于CD8 + T细胞识别肿瘤抗原至关重要。在黑色素瘤细胞中已发现，由于β2-微球蛋白基因缺陷导致HLA I类抗原表达缺失。为了进一步评估肿瘤逃逸机制，通过使用等位基因特异性单克隆抗体的流式细胞术分析，比较了24种转移性黑色素瘤细胞系和20种黑素细胞株中HLA I类抗原的表达。未发现HLA I类抗原表达完全缺失的情况；相反，发现了两种相对常见的现象：1）黑色素瘤细胞系和黑素细胞中HLA - B抗原的表达程度各不相同；然而，HLA - A抗原在所有细胞类型中均持续表达。此外，在从6例转移性黑色素瘤患者获得的6个冰冻切片标本中，仅在其中1个标本中检测到HLA - B位点抗原的体内表达。2）在14个HLA - A2（14%）黑色素瘤细胞系中的2个以及3个HLA - A29（33%）黑色素瘤细胞系中的1个中发现等位基因表达缺失，且包括一个完整的单倍型，这表明基因组片段缺失。等位基因特异性PCR扩增显示MHC II类、III类和I类区域内处于连锁不平衡状态的基因发生缺失。在体外模型中评估MHC限制现象时，应考虑肿瘤细胞系中HLA I类表达的异常情况。
