STIMULATION OF HLA-A,B,C BY IFN-ALPHA - THE DERIVATION OF MOLT-4 VARIANTS AND THE DIFFERENTIAL EXPRESSION OF HLA-A,B,C SUBSETS
STIMULATION OF HLA-A,B,C BY IFN-ALPHA - THE DERIVATION OF MOLT-4 VARIANTS AND THE DIFFERENTIAL EXPRESSION OF HLA-A,B,C SUBSETS
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DOI：
10.1002/j.1460-2075.1985.tb04014.x
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发表时间：
1985-01-01
期刊：
影响因子：
11.4
通讯作者：
MILSTEIN, C
中科院分区：
文献类型：
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作者：
BURRONE, OR;KEFFORD, RF;MILSTEIN, C
对干扰素-α具有改变的HLA-A、B、C应答的自发突变体（IFN-α）分离自人胸腺白血病细胞系Molt-4。使用异硫氰酸荧光素（FITC）-缀合的W6/32（HLA-A、B、C的单克隆抗体）和荧光激活的细胞分选仪，在IFN-α 24 - 48小时后具有最高和最低荧光的细胞。选择并扩大治疗。在几个选择循环后，获得了具有低（>野生型的10%）和高（好三倍）应答的突变体克隆。采用类似的方案用单克隆抗体YT 76衍生高应答突变体，所述单克隆抗体YT 76识别由IFN-α强烈诱导的HLA亚群。衍生稳定克隆，其中YT-HLA诱导是Molt 4细胞的7倍，并且其中HLA诱导在低100倍的IFN-α浓度下发生。突变体的高应答表型不伴随HLA-A、B、C的组成型表达水平的显著增加（在不存在IFN的情况下）。IFN-α治疗后HLA-A、B、C表达水平的增加治疗的主要原因是HLA分子亚群表达的增加，这是由包括HLA-B分子的单克隆抗体YT 76检测到的。
Spontaneous mutants with altered HLA-A,B,C response to interferon-.alpha. (IFN-.alpha.) were isolated from the human thymus leukemia cell line Molt-4. Using fluorescein isothiocyanate (FITC)-conjugated W6/32 (a monoclonal antibody to HLA-A,B,C) and the fluorescence-activated cell sorter, the cells with highest and lowest fluorescence after 24-48 h of IFN-.alpha. treatment were selected and expanded. After several cycles of selection, mutant clones with low (> 10% of wild-type) and high (three times better) response were obtained. A similar protocol was employed to derive high responder mutants with the monoclonal antibody YT76, which recognises a subset of HLA strongly induced by IFN-.alpha.. Stable clones were derived for which YT-HLA induction was 7-fold that of Molt 4 cells and for which HLA induction occurred at 100-fold lower concentrations of IFN-.alpha.. The high response phenotype of the mutants was not accompanied by a significant increase in the constitutive level of expression of HLA-A,B,C (in the absence of IFN). The increase in the level of HLA-A,B,C expression after IFN-.alpha. treatment is mostly accounted for by the increase in the expression of a subset of HLA molecules, detected by the monoclonal antibody YT76 including HLA-B molecules.