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Glycopeptide epitope facilitates HIV-1 envelope specific humoral immune responses by eliciting T cell help.


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.

SUBMITTER: Sun L 

PROVIDER: S-EPMC7242320 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Glycopeptide epitope facilitates HIV-1 envelope specific humoral immune responses by eliciting T cell help.

Sun Lina L   Paschall Amy V AV   Middleton Dustin R DR   Ishihara Mayumi M   Ozdilek Ahmet A   Wantuch Paeton L PL   Aceil Javid J   Duke Jeremy A JA   LaBranche Celia C CC   Tiemeyer Michael M   Avci Fikri Y FY  

Nature communications 20200521 1


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<sup>+</sup> 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 glyc  ...[more]

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