title: Tfh cells and HIV bnAbs, an immunodominance model of the HIV neutralizing antibody generation problem.
abstract: The generation of HIV bnAbs may be one of the greatest feats of the human immune system and our best hope of finally creating an HIV vaccine. The striking amount of somatic hypermutation in HIV bnAbs led to the hypothesis that T follicular helper (Tfh) cells and germinal centers (GC) play a critical role in the ability of the immune system to generate these uncommon antibodies. In this review, we first summarize what is known about the immunological process of HIV bnAb development, the challenges of eliciting bnAbs via immunizations, and the putative central roles of Tfh cells and GC in the generation of HIV bnAbs. Next, we explore factors that have impeded our understanding of the GC and Tfh-cell processes involved in bnAb generation, including the difficulty of quantifying antigen-specific GC Tfh cells and the difficulty of tracking GC in human and non-human primate vaccine studies. Finally, we discuss antibody immunodominance pertaining to neutralizing antibody generation and the GC response, propose models to explain the negative effects of immunodominance on neutralizing antibody generation, and consider means of optimizing Tfh and GC responses to potentially overcome these problems.
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.|Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Havenar-Daughton
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.|Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA, USA.
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.|Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA, USA.|Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Shane
authors.identifier: 0000-0002-6484-6262
authors.initials: S
authors.lastname: Crotty
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D018858:Germinal Center / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D011323:Primates; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000821:virology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D016056:Immunodominant Epitopes
keywords: Tfh cells; Vaccination; germinal centers