Universität zu Köln

Pusnik, Jernej, Fischinger, Stephanie, Dittmer, Ulf, Esser, Stefan, van Gils, Marit J., Sanders, Rogier W., Alter, Galit and Streeck, Hendrik ORCID: 0000-0002-0335-6390 (2021). Production of HIV-1 Env-Specific Antibodies Mediating Innate Immune Functions Depends on Cognate Interleukin-21-Secreting CD4(+) T Cells. J. Virol., 95 (8). WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5514

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Abstract

Antibodies with a functional Fc region were previously associated with protection from HIV-1 acquisition and spontaneous suppression of viral replication. Unlike broadly neutralizing antibodies, they are not restricted to neutralizing epitopes and do not require unconventional structural traits to exert their antiviral activity. They therefore develop earlier after infection and can be detected in the majority of cases. The conditions under which these antibodies are generated, however, remain largely unknown. Here, we demonstrate that the generation of HIV-1 Env-specific antibodies facilitating Fc-dependent innate immune responses, including neutrophil phagocytosis (ADNP), complement deposition (ADCD), and NK cell activation, likely depends on help provided by CD4(+)T and peripheral T follicular helper (pTfh) cells secreting interleukin21 (IL-21). Other proteins, including CD40L, gamma interferon (IFN-gamma), and IL-4/13, involved in cross talk between B and T cells were linked to the production of antibodies with a functional Fc region but only when coexpressed with IL-21. As a potential source of these antibodies, we identified a subset of Env-specific memory B cells known to be expanded in chronic HIV-1 infection. The frequency and level of Blimp-1 expression in Env-specific tissue-like memory B cells (TLM) correlated with the functional CD4(+)T cell subsets associated with robust antibody-dependent innate responses. Thus, our data suggest a mechanism responsible for the generation of antibodies with functional Fc region in chronically HIV-1-infected individuals that is based on CD4(+)T cell-induced activation of memory B cells. IMPORTANCE To develop a vaccine or immunotherapy that would cure the HIV-1 infection, it is important to identify helper T cells able to mount an efficient antibody response. Here, we demonstrate that the generation of HIV-1 Env-specific antibodies facilitating antibody-dependent innate immune responses likely depends on Env-specific IL-21-secreting CD4(+)T and peripheral T follicular helper cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pusnik, Jernej UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischinger, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Dittmer, Ulf UNSPECIFIED UNSPECIFIED UNSPECIFIED Esser, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED van Gils, Marit J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sanders, Rogier W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alter, Galit UNSPECIFIED UNSPECIFIED UNSPECIFIED Streeck, Hendrik UNSPECIFIED orcid.org/0000-0002-0335-6390 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-594914
DOI:	10.1128/JVI.02097-20
Journal or Publication Title:	J. Virol.
Volume:	95
Number:	8
Date:	2021
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-5514
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59491