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.
Authors	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
Journal	Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 2550 (05 21 2020) ISSN: 2041-1723 [Electronic] England
PMID	32439962 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Antibodies, Neutralizing Cytokines Epitopes, T-Lymphocyte Glycopeptides HIV Antibodies HIV Envelope Protein gp120 Histocompatibility Antigens Class II Polysaccharides
Topics	Amino Acid Sequence Animals Antibodies, Neutralizing (immunology) CD4-Positive T-Lymphocytes (immunology) Cytokines (metabolism) Epitopes, T-Lymphocyte (chemistry, immunology) Glycopeptides (chemistry, immunology) HIV Antibodies (immunology) HIV Envelope Protein gp120 (immunology) HIV-1 (immunology) Histocompatibility Antigens Class II (immunology) Immunity, Cellular Immunity, Humoral (immunology) Immunization Mice Polysaccharides (immunology) Th17 Cells (immunology) Th2 Cells (immunology)

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