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Abstract
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.
Highlights
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 human immunodeficiency virus-1 (HIV-1) envelope (Env) glycoprotein
Glycopeptide stimulation modulates T helper (Th) cell differentiation programming. These glycopeptide-specific CD4+ T cells play an important role in helping the humoral immune response to the HIV-1 envelope glycoprotein, which indicates that initiating potent CD4+ T cell responses by glycopeptide epitopes may be an important component of future HIV-1 vaccine strategies
For generation of immunogens enriched for glycopeptide epitopes, digestion of JR-FL gp[120] by endoproteinase GluC was followed by chromatographic separation and lectin selection (Supplementary Fig. 1a)
Summary
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. We report that a CD4+ T cell repertoire recognizes a glycopeptide epitope on gp[120] presented by MHCII pathway This glycopeptide is strongly immunogenic in eliciting glycan-dependent cellular and humoral immune responses. Despite broad appreciation that glycosylation of HIV-1 gp[120] influences the repertoire of antibody responses elicited in infected individuals and that the epitopes recognized by many bNAbs are glycan dependent, the importance of glycopeptides as non-conventional MHC ligands for generating T cell-mediated immunity to HIV-1 has not been addressed[6,7,8]. Glycopeptide stimulation modulates T helper (Th) cell differentiation programming These glycopeptide-specific CD4+ T cells play an important role in helping the humoral immune response to the HIV-1 envelope glycoprotein, which indicates that initiating potent CD4+ T cell responses by glycopeptide epitopes may be an important component of future HIV-1 vaccine strategies
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