Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, 414 E. Clark St, Vermillion, SD, 57069, USA.
Department of Public Health, School of Health Sciences, University of South Dakota, Vermillion, SD, 57069, USA.
Immunogenetics. 2018 Feb;70(2):99-113. doi: 10.1007/s00251-017-1021-7. Epub 2017 Jul 22.
CD8 T lymphocytes can reduce the production of human immunodeficiency virus 1 (HIV-1) by CD4 T cells by cytotoxic and non-cytotoxic mechanisms. To investigate the involvement of human leukocyte antigen (HLA) class I compatibility in anti-HIV responses, we co-cultured primary CD8 T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4 T cells. Altogether, CD8 T cell anti-HIV activity was evaluated in more than 200 co-cultures. Marked heterogeneity in HIV-1 replication levels was observed among the co-cultures sharing a common CD8 T cell source. The co-cultures that exhibited greater than 50% reduction in HIV production were found to have significantly increased numbers of matching HLA class I alleles (Yates chi-square = 54.21; p < 0.001). With CD8 T cells from HIV controllers and asymptomatic viremic individuals, matching HLA-B and/or HLA-C alleles were more predictive of strong anti-HIV activity than matching HLA-A alleles. Overall, HLA class I genotype matches were more closely associated with CD8 T cell anti-HIV activity than supertype pairings. Antibodies against HLA class I and CD3 reduced the CD8 T cell anti-HIV activity. Stimulated CD8 T cells exhibited increased anti-HIV activity and reduced dependency on HLA compatibility. These findings provide evidence that the maximal suppression of HIV replication by CD8 T cells requires the recognition of multiple epitopes. These studies provide insight for HIV vaccine development, and the analytic approach can be useful for the functional characterization of HLA class I alleles and tentative HLA class I supertypes.
CD8 T 细胞可通过细胞毒性和非细胞毒性机制减少 CD4 T 细胞中人类免疫缺陷病毒 1 (HIV-1) 的产生。为了研究人类白细胞抗原 (HLA) Ⅰ类相容性在抗 HIV 反应中的作用，我们将从 HIV-1 感染者外周血中分离的原代 CD8 T 细胞与同种异体和异源急性 HIV-1 感染的原代 CD4 T 细胞进行共培养。在 200 多个共培养物中评估了 CD8 T 细胞的抗 HIV 活性。在具有共同 CD8 T 细胞来源的共培养物中，观察到 HIV-1 复制水平存在明显的异质性。在 HIV 产生减少超过 50%的共培养物中，发现匹配的 HLA Ⅰ类等位基因数量显著增加（Yates 卡方=54.21;p<0.001）。对于 HIV 控制器和无症状病毒血症个体的 CD8 T 细胞，与 HLA-A 等位基因匹配相比，与 HLA-B 和/或 HLA-C 等位基因匹配更能预测强烈的抗 HIV 活性。总体而言，与 HLA Ⅰ类基因型匹配相比，超型配对与 CD8 T 细胞抗 HIV 活性的相关性更密切。针对 HLA Ⅰ类和 CD3 的抗体降低了 CD8 T 细胞的抗 HIV 活性。刺激的 CD8 T 细胞表现出增强的抗 HIV 活性和对 HLA 相容性的依赖性降低。这些发现为 CD8 T 细胞对 HIV 复制的最大抑制需要识别多个表位提供了证据。这些研究为 HIV 疫苗的开发提供了依据，并且该分析方法可用于 HLA Ⅰ类等位基因的功能特征分析和暂定 HLA Ⅰ类超型的分析。
