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.

Details

Title
Glycopeptide epitope facilitates HIV-1 envelope specific humoral immune responses by eliciting T cell help
Author
Sun, Lina 1 ; Paschall, Amy V 1 ; Middleton, Dustin R 1 ; Ishihara Mayumi 2 ; Ozdilek Ahmet 1 ; Wantuch, Paeton L 1 ; Javid, Aceil 1 ; Duke, Jeremy A 1 ; LaBranche, Celia C 3 ; Tiemeyer, Michael 4 ; Avci, Fikri Y 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) 
 University of Georgia, Complex Carbohydrate Research Center, Athens, USA (GRID:grid.213876.9) (ISNI:0000 0004 1936 738X) 
 Duke University, Department of Surgery, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961) 
 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) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2405596019
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.