Wang Z, Cao Y, Albino A P, Zeff R A, Houghton A, Ferrone S
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
J Clin Invest. 1993 Feb;91(2):684-92. doi: 10.1172/JCI116249.
The lack of HLA class I antigen expression by the melanoma cell line SK-MEL-33 is caused by a unique lesion in beta 2-microglobulin (beta 2-mu). Sequencing of beta 2-mu mRNA detected a guanosine deletion at position 323 in codon 76 that causes a frameshift with a subsequent introduction of a stop codon at a position 54 base upstream of the normal position of the stop codon in the message. The loss of 18 amino acids and the change of 6 amino acids, including a cysteine at position 80 in the carboxy terminus of beta 2-mu, are likely to cause marked changes in the structure of the polypeptide. The latter may account for the inability of beta 2-mu to associate with HLA class I heavy chains and for its lack of reactivity with the anti-beta 2-mu mAb tested. HLA class I antigen expression on SK-MEL-33 cells was reconstituted after transfection with a wild-type B2m gene, therefore indicating that the abnormality of endogenous B2m gene is the only mechanism underlying lack of HLA class I antigen expression by SK-MEL-33 cells. The guanosine deletion in B2m gene was detected also in the melanoma tissue from which SK-MEL-33 cells had originated. Therefore, the molecular lesion identified in the SK-MEL-33 melanoma cell line is not caused by a mutation acquired during growth in vitro but is likely to reflect a somatic mutation during tumor progression.
黑色素瘤细胞系SK-MEL-33缺乏HLA I类抗原表达是由β2-微球蛋白（β2-mu）中的独特损伤所致。对β2-mu mRNA进行测序时，在密码子76的第323位检测到一个鸟苷缺失，这导致了移码，随后在该信息中正常终止密码子位置上游54个碱基处引入了一个终止密码子。β2-mu羧基末端18个氨基酸的缺失和6个氨基酸的改变，包括第80位的半胱氨酸，可能会导致多肽结构发生显著变化。后者可能解释了β2-mu无法与HLA I类重链结合以及其与所测试的抗β2-mu单克隆抗体缺乏反应性的原因。用野生型B2m基因转染后，SK-MEL-33细胞上的HLA I类抗原表达得以重建，因此表明内源性B2m基因的异常是SK-MEL-33细胞缺乏HLA I类抗原表达的唯一潜在机制。在SK-MEL-33细胞所源自的黑色素瘤组织中也检测到了B2m基因中的鸟苷缺失。因此，在SK-MEL-33黑色素瘤细胞系中鉴定出的分子损伤并非由体外生长过程中获得的突变引起，而是可能反映了肿瘤进展过程中的体细胞突变。
