Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, 30602, USA.
Center for Molecular Medicine, University of Georgia, Athens, GA, 30602, USA.
Nat Commun. 2020 May 21;11(1):2550. doi: 10.1038/s41467-020-16319-0.
The inherent molecular complexity of human pathogens requires that mammals evolved an adaptive immune system equipped to handle presentation of non-conventional MHC ligands derived from disease-causing agents, such as HIV-1 envelope (Env) glycoprotein. Here, we report that a CD4 T cell repertoire recognizes a glycopeptide epitope on gp120 presented by MHCII pathway. This glycopeptide is strongly immunogenic in eliciting glycan-dependent cellular and humoral immune responses. The glycopeptide specific CD4 T cells display a prominent feature of Th2 and Th17 differentiation and exert high efficacy and potency to help Env trimer humoral immune responses. Glycopeptide-induced CD4 T cell response prior to Env trimer immunization elicits neutralizing antibody development and production of antibodies facilitating uptake of immunogens by antigen-presenting cells. Our identification of gp120 glycopeptide-induced, T cell-specific immune responses offers a foundation for developing future knowledge-based vaccines that elicit strong and long-lasting protective immune responses against HIV-1 infection.
人类病原体的固有分子复杂性要求哺乳动物进化出一种适应性免疫系统，以处理来自致病因子的非常规 MHC 配体的呈递，例如 HIV-1 包膜 (Env) 糖蛋白。在这里，我们报告说，CD4 T 细胞库识别由 MHCII 途径呈递的 gp120 上的糖肽表位。该糖肽在引发依赖聚糖的细胞和体液免疫反应方面具有很强的免疫原性。该糖肽特异性 CD4 T 细胞表现出 Th2 和 Th17 分化的突出特征，并发挥高效和强效作用，有助于增强Env 三聚体体液免疫反应。在Env 三聚体免疫之前诱导的糖肽 CD4 T 细胞反应引发中和抗体的产生和产生促进抗原呈递细胞摄取免疫原的抗体。我们鉴定出 gp120 糖肽诱导的 T 细胞特异性免疫反应为开发基于知识的疫苗奠定了基础，这些疫苗可以引发针对 HIV-1 感染的强烈和持久的保护性免疫反应。
