Glycopeptide epitope facilitates HIV-1 envelope specific humoral immune responses by eliciting T cell help.
Glycopeptide epitope facilitates HIV-1 envelope specific humoral immune responses by eliciting T cell help.
复制标题
糖肽表位通过引发 T 细胞帮助来促进 HIV-1 包膜特异性体液免疫反应。
DOI：
10.1038/s41467-020-16319-0
复制
发表时间：
2020
影响因子：
16.6
通讯作者：
Avci,FikriY
中科院分区：
文献类型：
--
作者：
Sun,Lina;Paschall,AmyV;Middleton,DustinR;Ishihara,Mayumi;Ozdilek,Ahmet;Wantuch,PaetonL;Aceil,Javid;Duke,JeremyA;LaBranche,CeliaC;Tiemeyer,Michael;Avci,FikriY
人类病原体的固有分子复杂性要求哺乳动物进化出适应性免疫系统，该适应性免疫系统装备成处理源自致病剂的非常规MHC配体（例如HIV-1包膜（Env）糖蛋白）的呈递。在这里，我们报告说，CD 4 +T细胞库识别的糖肽表位上的MHCII途径提出的gp 120。这种糖肽在引发聚糖依赖性细胞和体液免疫应答中具有强烈的免疫原性。糖肽特异性CD 4 +T细胞显示出Th 2和Th 17分化的突出特征，并发挥高功效和效力来帮助Env三聚体体液免疫应答。Env三聚体免疫前糖肽诱导的CD 4 +T细胞应答促进中和抗体的产生和抗体的产生，从而促进抗原呈递细胞摄取免疫原。我们对gp 120糖肽诱导的T细胞特异性免疫应答的鉴定为开发未来基于知识的疫苗提供了基础，这些疫苗可引发针对HIV-1感染的强大且持久的保护性免疫应答。
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.