Department of Medicine, University of California, San Francisco, San Francisco, CA, United States.
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States.
Front Immunol. 2021 Mar 19;12:650028. doi: 10.3389/fimmu.2021.650028. eCollection 2021.
Variation within the HLA locus been shown to play an important role in the susceptibility to and outcomes of numerous infections, but its influence on immunity to malaria is unclear. Increasing evidence indicates that acquired immunity to is mediated in part by the cellular immune response, including NK cells, CD4 and CD8 T cells, and semi-invariant γδ T cells. HLA molecules expressed by these lymphocytes influence the epitopes recognized by -specific T cells, and class I HLA molecules also serve as ligands for inhibitory receptors including KIR. Here we assessed the relationship of HLA class I and II alleles to the risk of infection and symptomatic malaria in a cohort of 892 Ugandan children and adults followed prospectively via both active and passive surveillance. We identified two HLA class I alleles, HLA-B53:01 and HLA-C06:02, that were associated with a higher prevalence of infection. Notably, no class I or II HLA alleles were found to be associated with protection from parasitemia or symptomatic malaria. These findings suggest that class I HLA plays a role in the ability to restrict parasitemia, supporting an essential role for the cellular immune response in immunity. Our findings underscore the need for better tools to enable mechanistic studies of the T cell response to at the epitope level and suggest that further study of the role of HLA in regulating pre-erythrocytic stages of the life cycle is warranted.
HLA 基因座内的变异已被证明在多种感染的易感性和结局中发挥重要作用，但它对疟疾免疫的影响尚不清楚。越来越多的证据表明，对疟疾的获得性免疫部分由细胞免疫反应介导，包括 NK 细胞、CD4 和 CD8 T 细胞和半不变 γδ T 细胞。这些淋巴细胞表达的 HLA 分子影响特异性 T 细胞识别的表位，而 I 类 HLA 分子也作为包括 KIR 在内的抑制性受体的配体。在这里，我们通过主动和被动监测前瞻性地随访了 892 名乌干达儿童和成人的队列，评估了 HLA I 类和 II 类等位基因与感染疟疾风险和症状性疟疾的关系。我们确定了两个与更高感染率相关的 HLA I 类等位基因，HLA-B53:01 和 HLA-C06:02。值得注意的是，没有发现 I 类或 II 类 HLA 等位基因与防止寄生虫血症或症状性疟疾有关。这些发现表明，I 类 HLA 在限制寄生虫血症方面发挥作用，支持细胞免疫反应在疟疾免疫中的重要作用。我们的研究结果强调需要更好的工具来实现对疟原虫 T 细胞反应的表位水平的机制研究，并表明需要进一步研究 HLA 在调节疟原虫生命周期的红细胞前期阶段中的作用。
