Secretion of HLA-A and -B antigens via an alternative RNA splicing pathway.
Secretion of HLA-A and -B antigens via an alternative RNA splicing pathway.
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DOI：
10.1084/jem.163.5.1173
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发表时间：
1986-05-01
期刊：
影响因子：
--
通讯作者：
Krangel MS
中科院分区：
文献类型：
--
作者：
Krangel MS
人类I类主要组织相容性抗原（HLA-A， -B和-C）是完整的膜蛋白异二聚体，它们通过重链羧基末端附近的一段疏水氨基酸锚定在膜上。先前的研究表明，由于RNA剪接模式从成熟的编码HLA-A2的转录本中去除外显子5（编码跨膜疏水氨基酸），诱变细胞系分泌一种水溶性形式的HLA-A2抗原。目前的研究是为了评估类似的过程是否可能在未突变的细胞中起作用。研究表明，T白血病细胞系hhb - all分泌水溶性I类分子（主要是HLA-A24），可选剪接去除部分HLA-A24编码转录物的外显子5。进一步表明，I类分子可能以等位基因特异性的方式从多种肿瘤细胞和正常细胞中分泌。这些发现与先前报道的人血清HLA-A和-B抗原之间的可能关系进行了讨论。
Human class I major histocompatibility antigens (HLA-A, -B and -C) are integral membrane protein heterodimers, which are anchored in the membrane via a stretch of hydrophobic amino acids near the carboxyl terminus of the heavy chain. It has previously been shown that a mutagenized cell line secretes a water soluble form of the HLA-A2 antigen, due to a pattern of RNA splicing that removes exon 5 (encoding the transmembrane hydrophobic amino acids) from mature, HLA-A2-- encoding transcripts. The present study was undertaken to assess whether a similar process might be operative in nonmutagenized cells. It is shown that water soluble class I molecules (primarily HLA-A24) are secreted by the T leukemic cell line HPB-ALL, and that alternative splicing removes exon 5 from a fraction of HLA-A24--encoding transcripts. It is further shown that class I molecules are secreted, possibly in an allele-specific fashion, from a variety of tumor cells and normal cells. The possible relationship between these findings and previous reports of HLA-A and -B antigens in human serum is discussed.