IMPAIRED ASSEMBLY AND TRANSPORT OF HLA-A AND HLA-B ANTIGENS IN A MUTANT TXB CELL HYBRID
IMPAIRED ASSEMBLY AND TRANSPORT OF HLA-A AND HLA-B ANTIGENS IN A MUTANT TXB CELL HYBRID
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DOI：
10.1002/j.1460-2075.1986.tb04307.x
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发表时间：
1986-05-01
期刊：
影响因子：
11.4
通讯作者：
CRESSWELL, P
中科院分区：
文献类型：
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作者：
SALTER, RD;CRESSWELL, P
HLA I类抗原的生物合成已在一株变异B-LCLxT-LCL杂交株174XCEM .cntdot中进行了研究。T2。该细胞系编码HLA-A2和-B5，但在细胞表面仅表达少量A2抗原和无法检测到的B5抗原，这是由于在人类主要组织相容性复合体II类区域编码的反式作用调节基因的突变失活。hla -a和hla - b特异性探针的Northern blot分析显示，174XCEMT。T2合成的A和B基因座mRNA数量与其ⅰ类抗原阳性亲本细胞系相当。免疫沉淀研究表明：174XCEM。T2合成正常HLA重链和。β。不能形成二聚体的2微球蛋白。重链通常是n -糖基化的，但不会发生聚糖到复合物形式的加工。此外，该细胞系中的游离重链不被磷酸化。因此，174XCEM中的大多数I级重链。T2不与。结合。2-微球蛋白，不会被加工或运输到细胞表面。由于这两个亚基都是正常合成的，我们认为174XCEM中缺少一个额外的分子。由hla连接基因编码的T2是有效组装I类抗原亚基所必需的。
Biosynthesis of HLA class I antigens has been studied in a variant B-LCLxT-LCL hybrid, 174XCEM .cntdot. T2. This cell line encodes HLA-A2 and -B5, but expresses only small amounts of A2 antigen and undetectable B5 antigen at the cell surface due to a mutation inactivating a trans-acting regulatory gene encoded within the class II region of the human major histocompatbility complex. Northern blot analysis with HLA-A-and HLA-B-specific probes shows that 174XCEMT.T2 synthesizes quantities of A and B locus mRNA comparable with its class I antigen-positive parent cell line. Immune precipitation studies indicate that 174XCEM.T2 synthesizes normal HLA heavy chains and .beta.2-microglobulin which fail to form dimers. The heavy chains are N-glycosylated normally, but processing of the glycan to the complex form does not occur. In addition, free heavy chains in this cell line are not phosphorylated. Thus, the majority of class I heavy chains in 174XCEM.T2 do not combine with .beta.2-microglobulin, and are not processed or transported to the cell surface. As both subunits are synthesized in normal amounts, we propose that an additional molecule absent from 174XCEM.T2 and encoded by an HLA-linked gene is necessary for efficient assembly of class I antigen subunits.