Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin.

We compared the effects of adoptively transferred Th cell clones specific for the influenza hemagglutinin (HA), matrix (M), or nucleoprotein (NP) on the antibody response of nude mice infected with A/PR/8/34 influenza virus. We show that the production of antibodies to the HA absolutely requires the presence of virus-specific Th cells. Further, transfer of a Th clone specific for the internal proteins, M or NP, was as effective as was transfer of an HA-specific clone in supporting an antibody response to the HA. With each of the clones, the kinetics of the response were accelerated by approximately 3 d compared with the antibody response of normal BALB/c mice. The HA- and M-specific clones supported an isotype switch from IgM to IgG and IgA similar to that which occurs during a normal antibody response. Finally, as shown by coinfection experiments, the response required a cognate T-B interaction whether the determinants recognized by the Th and B cell are located on the same viral protein or on different viral proteins within the same virus particle. The implications of these findings for understanding the T-B interactions that occur during an effective antiviral antibody response are discussed.