DKMS Life Science Lab, Dresden, Germany.
DKMS, Tübingen, Germany.
HLA. 2021 May;97(5):389-398. doi: 10.1111/tan.14195. Epub 2021 Feb 16.
HLA-E is a member of the nonclassical HLA class Ib genes. Even though it is structurally highly similar to the classical HLA class Ia genes, it is less diverse and only 45 alleles and 12 proteins were known in December 2019 (IPD-IMGT/HLA, release 3.38.0). Since 2017, we have genotyped over 3 million voluntary stem cell donors for HLA-E by sequencing the most relevant allele-determining bases of exons 2 and 3. As expected, most donors harbor the two predominant alleles HLA-E01:01 and/or HLA-E01:03. However, in 1666 (0.05%) of our samples we detected 345 distinct novel HLA-E sequences. The most frequent one was identified in 162 samples and has by now been named HLA-E*01:114. To characterize these novel alleles in full-length, we used both short-read Illumina and long-read PacBio sequencing to obtain fully phased and highly accurate sequences. This resulted in 234 submissions to IPD-IMGT/HLA comprising 170 novel HLA-E alleles, which encode for 93 novel HLA-E proteins, as well as 64 confirmations or sequence extensions. Consequently, the number of HLA-E alleles in the database (release 3.42.0) has now increased to 256 HLA-E alleles and 110 HLA-E proteins.
HLA-E 是人类白细胞抗原（HLA）非经典 I 类基因亚群的一员。尽管其结构与经典 HLA I 类基因高度相似，但 HLA-E 的多样性较低，截至 2019 年 12 月，仅已知 45 个等位基因和 12 种蛋白（IPD-IMGT/HLA，版本 3.38.0）。自 2017 年以来，我们通过对exon2 和 exon3 中与等位基因决定相关的关键碱基进行测序，对超过 300 万例自愿捐献的干细胞供者进行 HLA-E 基因分型。正如预期的那样，大多数供者携带两种主要的等位基因 HLA-E01:01 和/或 HLA-E01:03。然而，在我们的 300 多万例样本中，有 1666 例（0.05%）检测到 345 种独特的新 HLA-E 序列。其中最常见的一种在 162 个样本中被发现，目前已被命名为 HLA-E*01:114。为了全面描述这些新的等位基因，我们同时使用短读 Illumina 和长读 PacBio 测序来获得完全定相和高度准确的序列。这导致有 234 个 HLA-E 等位基因序列提交到 IPD-IMGT/HLA，其中包括 170 个新的 HLA-E 等位基因，这些等位基因编码 93 种新的 HLA-E 蛋白，以及 64 个确认或序列扩展。因此，数据库（版本 3.42.0）中 HLA-E 等位基因的数量现已增加到 256 个 HLA-E 等位基因和 110 个 HLA-E 蛋白。
