Major histocompatibility complex class II (HLA-DRB and -DQB) allele frequencies in Botswana: association with human immunodeficiency virus type 1 infection.

Thumbi Ndung'u, Simani Gaseitsiwe, Enoch Sepako, Florence Doualla-Bell, Trevor Peter, Soyeon Kim, Ibou Thior, Vladimir A Novitsky, Max Essex
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Abstract

Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Botswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Botswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs.

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博茨瓦纳主要组织相容性复合体 II 类(HLA-DRB 和 -DQB)等位基因频率:与人体免疫缺陷病毒 1 型感染的关系。
由于 1 型人类免疫缺陷病毒(HIV-1)的高流行率,南部非洲正面临着前所未有的公共卫生危机。目前正在进行主要基于诱导 HIV 特异性 T 细胞的疫苗开发和测试工作。为了了解人类白细胞抗原(HLA)II 类等位基因在 HIV 发病机制中的作用,并促进基于 HLA 的 HIV-1 疫苗设计,我们分析了南部非洲国家博茨瓦纳境内 HLA II 类等位基因的频率。通过对 DRB 和 DQB1 位点进行分子基因分型,确定了博茨瓦纳人群中常见的 HLA II 类等位基因。DRB1等位基因群DRB1*01、DRB1*02/15、DRB1*03、DRB1*11和DRB1*13的频率超过20%。在 DQB1 基因座中,DQB1*06(47.7%)是最常见的等位基因群,其次是 DQB1*03(39.2%)和 DQB1*04(25.8%)。我们发现,DRB1*01 在 HIV 阴性个体中比在 HIV 阳性个体中更常见,而表达 DRB1*08 的个体的病毒载量中位数较低。我们证明,博茨瓦纳人群中某些 HLA II 类等位基因的频率与北美人群(包括非裔美国人)有很大不同。博茨瓦纳的常见等位基因群在其他非洲人群中占很大比例,可以作为地区疫苗设计的目标。
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