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Rabies superantigen as a Vbeta T-dependent adjuvant

Recently we reported evidence that nucleocapsid (NC) of rabies virus is a Vbeta8-specific exogenous superantigen (SAg) in humans and a Vbeta6- specific SAg in BALB/c mice. NC was also found to stimulate rabies vaccination by enhancing the rabies neutralizing antibody response. In this study, we test...

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Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1996
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192506/
https://www.ncbi.nlm.nih.gov/pubmed/8666920
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description Recently we reported evidence that nucleocapsid (NC) of rabies virus is a Vbeta8-specific exogenous superantigen (SAg) in humans and a Vbeta6- specific SAg in BALB/c mice. NC was also found to stimulate rabies vaccination by enhancing the rabies neutralizing antibody response. In this study, we tested the hypothesis that the stimulating effect of NC and its SAg properties are linked. To do this, we studied the effect of rabies SAg on the immune response to an unrelated antigen, the influenza virus, and compared the response in two congenic strains of mice, BALB/c and BALB/D2. BALB/c mice are rabies SAg responsive, whereas BALB/D2 mice are not responsive to SAg activation by rabies NC because they lack the SAg recognition element, the Vbeta6 T cell receptor. In BALB/c mice, coinjection of rabies SAg with inactivated influenza virus resulted in a rapid and long-term increase in (a) the titres of influenza virus-specific antibodies (IgG and IgM), including protective hemagglutination-inhibiting antibodies, (b) antigen-specific proliferation and, (c) IL-2 and IL-4 secretion by lymph node lymphocytes, when compared to mice that received influenza virus only. In contrast, in BALB/D2 mice, neither antibody nor lymphocyte responses were stimulated. Moreover, during establishment of the primary response, the increase in influenza-primed T cells was mainly restricted to those bearing a Vbeta6 TCR. These data establish that rabies SAg can stimulate both T and B cell-specific responses to an unrelated antigen, depending on expression of the SAg target (Vbeta6 T lymphocytes). This is the first report linking NC adjuvant properties with its SAg mechanism.
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spelling pubmed-21925062008-04-16 Rabies superantigen as a Vbeta T-dependent adjuvant J Exp Med Articles Recently we reported evidence that nucleocapsid (NC) of rabies virus is a Vbeta8-specific exogenous superantigen (SAg) in humans and a Vbeta6- specific SAg in BALB/c mice. NC was also found to stimulate rabies vaccination by enhancing the rabies neutralizing antibody response. In this study, we tested the hypothesis that the stimulating effect of NC and its SAg properties are linked. To do this, we studied the effect of rabies SAg on the immune response to an unrelated antigen, the influenza virus, and compared the response in two congenic strains of mice, BALB/c and BALB/D2. BALB/c mice are rabies SAg responsive, whereas BALB/D2 mice are not responsive to SAg activation by rabies NC because they lack the SAg recognition element, the Vbeta6 T cell receptor. In BALB/c mice, coinjection of rabies SAg with inactivated influenza virus resulted in a rapid and long-term increase in (a) the titres of influenza virus-specific antibodies (IgG and IgM), including protective hemagglutination-inhibiting antibodies, (b) antigen-specific proliferation and, (c) IL-2 and IL-4 secretion by lymph node lymphocytes, when compared to mice that received influenza virus only. In contrast, in BALB/D2 mice, neither antibody nor lymphocyte responses were stimulated. Moreover, during establishment of the primary response, the increase in influenza-primed T cells was mainly restricted to those bearing a Vbeta6 TCR. These data establish that rabies SAg can stimulate both T and B cell-specific responses to an unrelated antigen, depending on expression of the SAg target (Vbeta6 T lymphocytes). This is the first report linking NC adjuvant properties with its SAg mechanism. The Rockefeller University Press 1996-04-01 /pmc/articles/PMC2192506/ /pubmed/8666920 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Rabies superantigen as a Vbeta T-dependent adjuvant
title Rabies superantigen as a Vbeta T-dependent adjuvant
title_full Rabies superantigen as a Vbeta T-dependent adjuvant
title_fullStr Rabies superantigen as a Vbeta T-dependent adjuvant
title_full_unstemmed Rabies superantigen as a Vbeta T-dependent adjuvant
title_short Rabies superantigen as a Vbeta T-dependent adjuvant
title_sort rabies superantigen as a vbeta t-dependent adjuvant
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192506/
https://www.ncbi.nlm.nih.gov/pubmed/8666920