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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.
T cells recognize peptide antigens presented in the context of MHC but can additionally recognize non-conventional ligands. Here the authors show T cells specific for a HIV-1 associated glycopeptide antigen presented by MHC class II help envelope (Env) trimer induced humoral immune responses.
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1 University of Georgia, Department of Biochemistry and Molecular Biology, Athens, USA (GRID:grid.213876.9) (ISNI:0000 0004 1936 738X); University of Georgia, Center for Molecular Medicine, Athens, USA (GRID:grid.213876.9) (ISNI:0000 0004 1936 738X)
2 University of Georgia, Complex Carbohydrate Research Center, Athens, USA (GRID:grid.213876.9) (ISNI:0000 0004 1936 738X)
3 Duke University, Department of Surgery, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961)
4 University of Georgia, Department of Biochemistry and Molecular Biology, Athens, USA (GRID:grid.213876.9) (ISNI:0000 0004 1936 738X); University of Georgia, Complex Carbohydrate Research Center, Athens, USA (GRID:grid.213876.9) (ISNI:0000 0004 1936 738X)