RABIES SUPERANTIGEN AS A V-BETA T-DEPENDENT ADJUVANT

Recently we reported evidence that the nucleocapsid (NC) of rabies vir us is a V beta 8-specific exogenous superantigen (SAg) in humans and a V beta 6-specific SAg in BALB/c mice. NC was also found to stimulate rabies vaccination by enhancing the rabies neutralizing antibody respo nse. In this study, we tested the hypothesis that the stimulating effe ct 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 ill two congenic strain s of mice, BALB/c and BALB/D2. BALB/c mice are rabies SAS responsive, whereas BALB/D2 mice are not responsive to SAg activation by rabies NC because they lack the SAg recognition element, the V beta 6 T cell re ceptor. In BALB/c mice, coinjection of rabies SAg with inactivated inf luenza virus resulted in a rapid and long-term increase in (a) the tit res of influenza virus-specific antibodies (IgG and IgM), including pr otective hemagglutination-inhibiting antibodies, (b) antigen-specific proliferation and, (c) IL-2 and IL-4 secretion by lymph node lymphocyt es, when compared to mice that received influenza virus only. in contr ast, in BALB/D2 mice, neither antibody nor lymphocyte responses were s timulated. Moreover, during establishment oi the primary response, the increase in influenza-primed T cells was mainly restricted to those b earing a V beta 6 TCR. These data establish that rabies SAg can stimul ate both T and B cell-specific responses to an unrelated antigen, depe nding on expression of the SAg target (V beta 6 T lymphocytes). This i s the first report linking NC adjuvant properties with its SAg mechani sm.