Glycopeptide epitope facilitates HIV-1 envelope specific humoral immune responses by eliciting T cell help
Lina Sun, Amy V. Paschall, Dustin R. Middleton, Mayumi Ishihara, Ahmet Ozdilek, Paeton L. Wantuch, Javid Aceil, Jeremy A. Duke, Celia C. LaBranche, Michael Tiemeyer, Fikri Y. Avci
Abstract
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.