Control of HIV-1 by an HLA-B*52:01-C*12:02 Protective Haplotype
Control of HIV-1 by an HLA-B*52:01-C*12:02 Protective Haplotype
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DOI：
10.1093/infdis/jix483
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发表时间：
2017-12-01
影响因子：
6.4
通讯作者：
Takiguchi, Masafumi
中科院分区：
文献类型：
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作者：
Chikata, Takayuki;Murakoshi, Hayato;Takiguchi, Masafumi
HLA-B*52：01-C*12：02在大约20%的日本人中发现，众所周知与溃疡性结肠炎和大动脉炎有关。这种单倍型也被认为对感染人类免疫缺陷病毒（HIV）1型的个体具有保护作用。最近的研究表明，HLA-B*52：01限制的HIV-1特异性T细胞抑制HIV-1，HLA-C*12：02与KIR 2DL 2一起在自然杀伤细胞介导的HIV-1控制中发挥重要作用。然而，HLA-C*12：02限制性细胞毒性T淋巴细胞（CTL）在抑制HIV-1复制中的作用仍然未知。在本研究中，我们证明了HLA-C*12：02限制性CTL特异性的2个免疫显性表位，Pol IY 11和Nef MY 9，有助于抑制HIV-1感染者的HIV-1复制。进一步的分析表明，这2个HLA-C*12：02限制性CTL与4个HLA-B*52：01限制性CTL一起有效地抑制具有HLA-B*52：01-C*12：02单倍型的个体中的HIV-1。因此，HLA-C*12：02和HLA-B*52：01等位基因都有助于通过HIV-1特异性CTL和自然杀伤细胞抑制HIV-1。
HLA-B*52:01-C*12:02, which is found in approximately 20% of all Japanese persons, is well known to be associated with ulcerative colitis and Takayasu arteritis. This haplotype is also known to be protective in individuals infected with human immunodeficiency virus (HIV) type 1. Recent studies showed that HLA-B*52:01-restricted HIV-1-specific T cells suppress HIV-1 and that HLA-C*12:02 together with KIR2DL2 play an important role in natural killer cell-mediated control of HIV-1. However, the role of HLA-C*12:02-restricted cytotoxic T lymphocytes (CTLs) in suppressing HIV-1 replication remains unknown. In the present study, we demonstrated that HLA-C*12:02-restricted CTLs specific for 2 immunodominant epitopes, Pol IY11 and Nef MY9, contributed to the suppression of HIV-1 replication in HIV-1-infected individuals. Further analysis demonstrated that these 2 HLA-C*12:02-restricted CTLs together with 4 HLA-B*52:01-restricted ones effectively suppressed HIV-1 in individuals with the HLA-B*52:01-C*12:02 haplotype. Thus, both HLA-C*12:02 and HLA-B*52:01 alleles contribute to HIV-1 suppression via both HIV-1-specific CTLs and natural killer cells in individuals with this haplotype.